High-resolution crystal structure of the human CB1 cannabinoid receptor View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Zhenhua Shao, Jie Yin, Karen Chapman, Magdalena Grzemska, Lindsay Clark, Junmei Wang, Daniel M. Rosenbaum

ABSTRACT

The human cannabinoid G-protein-coupled receptors (GPCRs) CB1 and CB2 mediate the functional responses to the endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) and to the widely consumed plant phytocannabinoid Δ9-tetrahydrocannabinol (THC). The cannabinoid receptors have been the targets of intensive drug discovery efforts, because modulation of these receptors has therapeutic potential to control pain, epilepsy, obesity, and other disorders. Although much progress in understanding the biophysical properties of GPCRs has recently been made, investigations of the molecular mechanisms of the cannabinoids and their receptors have lacked high-resolution structural data. Here we report the use of GPCR engineering and lipidic cubic phase crystallization to determine the structure of the human CB1 receptor bound to the inhibitor taranabant at 2.6-Å resolution. We found that the extracellular surface of CB1, including the highly conserved membrane-proximal N-terminal region, is distinct from those of other lipid-activated GPCRs, forming a critical part of the ligand-binding pocket. Docking studies further demonstrate how this same pocket may accommodate the cannabinoid agonist THC. Our CB1 structure provides an atomic framework for studying cannabinoid receptor function and will aid the design and optimization of therapeutic modulators of the endocannabinoid system. More... »

PAGES

602

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature20613

DOI

http://dx.doi.org/10.1038/nature20613

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004912475

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27851727


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1115", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Pharmacology and Pharmaceutical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shao", 
        "givenName": "Zhenhua", 
        "id": "sg:person.01143530261.55", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01143530261.55"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yin", 
        "givenName": "Jie", 
        "id": "sg:person.0713053261.91", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0713053261.91"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chapman", 
        "givenName": "Karen", 
        "id": "sg:person.015627704151.30", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015627704151.30"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Grzemska", 
        "givenName": "Magdalena", 
        "id": "sg:person.016425264551.54", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016425264551.54"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Clark", 
        "givenName": "Lindsay", 
        "id": "sg:person.0735150755.29", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0735150755.29"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Green Center for Systems Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wang", 
        "givenName": "Junmei", 
        "id": "sg:person.013164203274.32", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013164203274.32"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rosenbaum", 
        "givenName": "Daniel M.", 
        "id": "sg:person.01154454461.00", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01154454461.00"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1107/s0907444910007493", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000235100"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1107/s0907444910007493", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000235100"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m109.041590", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000837944"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1215904", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001612051"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/mol.105.014407", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003875348"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0076-6879(97)76066-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004907170"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ejphar.2010.10.056", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005261719"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.181342398", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006228920"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m406648200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007615746"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2015.06.002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007717523"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/jpet.106.118737", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010052209"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/sj.bjp.0707442", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012111961"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jcc.20290", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012674250"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jcc.20290", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012674250"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1107/s0021889807021206", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012753217"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature07063", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013925337", 
          "https://doi.org/10.1038/nature07063"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ab.2016.01.016", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014374361"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ab.2016.01.016", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014374361"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/mol.62.6.1274", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014605409"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/mol.107.034645", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015093363"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/mol.64.3.570", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016016540"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/jpet.115.230151", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020034616"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nprot.2009.31", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021131005", 
          "https://doi.org/10.1038/nprot.2009.31"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nprot.2009.31", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021131005", 
          "https://doi.org/10.1038/nprot.2009.31"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2016.10.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021600730"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2016.10.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021600730"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2015.04.043", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022061079"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2015.04.043", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022061079"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1063545", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022454306"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m507394200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023750308"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1107/s0907444904019079", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023777325"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.pnpbp.2012.02.009", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023925597"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/mol.105.016162", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025529128"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev-psych-113011-143739", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026442853"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s11481-015-9600-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027008353", 
          "https://doi.org/10.1007/s11481-015-9600-6"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s11481-015-9600-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027008353", 
          "https://doi.org/10.1007/s11481-015-9600-6"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1107/s0907444904011679", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027804289"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi400842k", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028266288"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cmet.2012.07.002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031525295"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.neuropharm.2004.07.030", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032240792"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/srep33302", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033700432", 
          "https://doi.org/10.1038/srep33302"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m111.261651", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035209275"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1517/14728210902736568", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036202237"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm.3265", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037773319", 
          "https://doi.org/10.1038/nm.3265"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm0306430", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040469800"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm0306430", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040469800"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.289.5480.739", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042667522"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1150609", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043965657"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.nut.2010.11.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047086525"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m112.390955", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048271405"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/febs.12212", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048445470"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nsmb.3183", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049059057", 
          "https://doi.org/10.1038/nsmb.3183"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cpt.115", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050064250"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cpt.115", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050064250"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi060067k", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055201672"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi060067k", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055201672"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ja01062a046", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055765175"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm051256o", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055950056"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm051256o", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055950056"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm7014974", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055955374"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm7014974", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055955374"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1063/1.1332996", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1057695872"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1079343524", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2016-12", 
    "datePublishedReg": "2016-12-01", 
    "description": "The human cannabinoid G-protein-coupled receptors (GPCRs) CB1 and CB2 mediate the functional responses to the endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) and to the widely consumed plant phytocannabinoid \u03949-tetrahydrocannabinol (THC). The cannabinoid receptors have been the targets of intensive drug discovery efforts, because modulation of these receptors has therapeutic potential to control pain, epilepsy, obesity, and other disorders. Although much progress in understanding the biophysical properties of GPCRs has recently been made, investigations of the molecular mechanisms of the cannabinoids and their receptors have lacked high-resolution structural data. Here we report the use of GPCR engineering and lipidic cubic phase crystallization to determine the structure of the human CB1 receptor bound to the inhibitor taranabant at 2.6-\u00c5 resolution. We found that the extracellular surface of CB1, including the highly conserved membrane-proximal N-terminal region, is distinct from those of other lipid-activated GPCRs, forming a critical part of the ligand-binding pocket. Docking studies further demonstrate how this same pocket may accommodate the cannabinoid agonist THC. Our CB1 structure provides an atomic framework for studying cannabinoid receptor function and will aid the design and optimization of therapeutic modulators of the endocannabinoid system.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/nature20613", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.3859087", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1018957", 
        "issn": [
          "0090-0028", 
          "1476-4687"
        ], 
        "name": "Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "7634", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "540"
      }
    ], 
    "name": "High-resolution crystal structure of the human CB1 cannabinoid receptor", 
    "pagination": "602", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "176889481596e810ff536862303aa5a4964ac94cdf54d29167c3d19aeb6b69e3"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "27851727"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "0410462"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/nature20613"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1004912475"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/nature20613", 
      "https://app.dimensions.ai/details/publication/pub.1004912475"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T12:58", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000365_0000000365/records_71689_00000000.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/nature20613"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature20613'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature20613'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature20613'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature20613'


 

This table displays all metadata directly associated to this object as RDF triples.

272 TRIPLES      21 PREDICATES      80 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/nature20613 schema:about anzsrc-for:11
2 anzsrc-for:1115
3 schema:author Ndffc755022fa4f74831f62f3977f0f09
4 schema:citation sg:pub.10.1007/s11481-015-9600-6
5 sg:pub.10.1038/nature07063
6 sg:pub.10.1038/nm.3265
7 sg:pub.10.1038/nprot.2009.31
8 sg:pub.10.1038/nsmb.3183
9 sg:pub.10.1038/srep33302
10 https://app.dimensions.ai/details/publication/pub.1079343524
11 https://doi.org/10.1002/cpt.115
12 https://doi.org/10.1002/jcc.20290
13 https://doi.org/10.1016/j.ab.2016.01.016
14 https://doi.org/10.1016/j.cell.2015.04.043
15 https://doi.org/10.1016/j.cell.2015.06.002
16 https://doi.org/10.1016/j.cell.2016.10.004
17 https://doi.org/10.1016/j.cmet.2012.07.002
18 https://doi.org/10.1016/j.ejphar.2010.10.056
19 https://doi.org/10.1016/j.neuropharm.2004.07.030
20 https://doi.org/10.1016/j.nut.2010.11.003
21 https://doi.org/10.1016/j.pnpbp.2012.02.009
22 https://doi.org/10.1016/s0076-6879(97)76066-x
23 https://doi.org/10.1021/bi060067k
24 https://doi.org/10.1021/bi400842k
25 https://doi.org/10.1021/ja01062a046
26 https://doi.org/10.1021/jm0306430
27 https://doi.org/10.1021/jm051256o
28 https://doi.org/10.1021/jm7014974
29 https://doi.org/10.1038/sj.bjp.0707442
30 https://doi.org/10.1063/1.1332996
31 https://doi.org/10.1073/pnas.181342398
32 https://doi.org/10.1074/jbc.m109.041590
33 https://doi.org/10.1074/jbc.m111.261651
34 https://doi.org/10.1074/jbc.m112.390955
35 https://doi.org/10.1074/jbc.m406648200
36 https://doi.org/10.1074/jbc.m507394200
37 https://doi.org/10.1107/s0021889807021206
38 https://doi.org/10.1107/s0907444904011679
39 https://doi.org/10.1107/s0907444904019079
40 https://doi.org/10.1107/s0907444910007493
41 https://doi.org/10.1111/febs.12212
42 https://doi.org/10.1124/jpet.106.118737
43 https://doi.org/10.1124/jpet.115.230151
44 https://doi.org/10.1124/mol.105.014407
45 https://doi.org/10.1124/mol.105.016162
46 https://doi.org/10.1124/mol.107.034645
47 https://doi.org/10.1124/mol.62.6.1274
48 https://doi.org/10.1124/mol.64.3.570
49 https://doi.org/10.1126/science.1063545
50 https://doi.org/10.1126/science.1150609
51 https://doi.org/10.1126/science.1215904
52 https://doi.org/10.1126/science.289.5480.739
53 https://doi.org/10.1146/annurev-psych-113011-143739
54 https://doi.org/10.1517/14728210902736568
55 schema:datePublished 2016-12
56 schema:datePublishedReg 2016-12-01
57 schema:description The human cannabinoid G-protein-coupled receptors (GPCRs) CB1 and CB2 mediate the functional responses to the endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) and to the widely consumed plant phytocannabinoid Δ<sup>9</sup>-tetrahydrocannabinol (THC). The cannabinoid receptors have been the targets of intensive drug discovery efforts, because modulation of these receptors has therapeutic potential to control pain, epilepsy, obesity, and other disorders. Although much progress in understanding the biophysical properties of GPCRs has recently been made, investigations of the molecular mechanisms of the cannabinoids and their receptors have lacked high-resolution structural data. Here we report the use of GPCR engineering and lipidic cubic phase crystallization to determine the structure of the human CB1 receptor bound to the inhibitor taranabant at 2.6-Å resolution. We found that the extracellular surface of CB1, including the highly conserved membrane-proximal N-terminal region, is distinct from those of other lipid-activated GPCRs, forming a critical part of the ligand-binding pocket. Docking studies further demonstrate how this same pocket may accommodate the cannabinoid agonist THC. Our CB1 structure provides an atomic framework for studying cannabinoid receptor function and will aid the design and optimization of therapeutic modulators of the endocannabinoid system.
58 schema:genre research_article
59 schema:inLanguage en
60 schema:isAccessibleForFree true
61 schema:isPartOf N59d0e4d4e95c42f1a1230f1c0027c5b8
62 N822dc77f05664f82bed6c0461a6c3dd9
63 sg:journal.1018957
64 schema:name High-resolution crystal structure of the human CB1 cannabinoid receptor
65 schema:pagination 602
66 schema:productId N1037a030be1d4b0aaa86524c5a39a5a7
67 N256b104c2c224bcf9deedd76ce74e1f3
68 N4467ad17597b4e1ca60ec17e1ad47060
69 N76b379152fbb419090930c02eefc9326
70 Nb06dff34507e414089bfafa07b8dd1ef
71 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004912475
72 https://doi.org/10.1038/nature20613
73 schema:sdDatePublished 2019-04-11T12:58
74 schema:sdLicense https://scigraph.springernature.com/explorer/license/
75 schema:sdPublisher Nea61b5cfe66e4c81b0abd57eba6621d2
76 schema:url https://www.nature.com/articles/nature20613
77 sgo:license sg:explorer/license/
78 sgo:sdDataset articles
79 rdf:type schema:ScholarlyArticle
80 N1037a030be1d4b0aaa86524c5a39a5a7 schema:name pubmed_id
81 schema:value 27851727
82 rdf:type schema:PropertyValue
83 N256b104c2c224bcf9deedd76ce74e1f3 schema:name doi
84 schema:value 10.1038/nature20613
85 rdf:type schema:PropertyValue
86 N2f0003fe9e3947429dc8daaede5b40b4 rdf:first sg:person.013164203274.32
87 rdf:rest N4710d429bb8b405cace887d257ae1004
88 N4467ad17597b4e1ca60ec17e1ad47060 schema:name dimensions_id
89 schema:value pub.1004912475
90 rdf:type schema:PropertyValue
91 N4710d429bb8b405cace887d257ae1004 rdf:first sg:person.01154454461.00
92 rdf:rest rdf:nil
93 N48e3ee77b6e84f9f9712139289f08bb9 rdf:first sg:person.0713053261.91
94 rdf:rest Naa83a6ea4c4545039f7518d05edd5270
95 N59d0e4d4e95c42f1a1230f1c0027c5b8 schema:volumeNumber 540
96 rdf:type schema:PublicationVolume
97 N76b379152fbb419090930c02eefc9326 schema:name nlm_unique_id
98 schema:value 0410462
99 rdf:type schema:PropertyValue
100 N822dc77f05664f82bed6c0461a6c3dd9 schema:issueNumber 7634
101 rdf:type schema:PublicationIssue
102 Naa83a6ea4c4545039f7518d05edd5270 rdf:first sg:person.015627704151.30
103 rdf:rest Nb93e2fec23d844afab14e7be6e8eae25
104 Nb06dff34507e414089bfafa07b8dd1ef schema:name readcube_id
105 schema:value 176889481596e810ff536862303aa5a4964ac94cdf54d29167c3d19aeb6b69e3
106 rdf:type schema:PropertyValue
107 Nb93e2fec23d844afab14e7be6e8eae25 rdf:first sg:person.016425264551.54
108 rdf:rest Ne27d19aed228437796d5fbc9becfd241
109 Ndffc755022fa4f74831f62f3977f0f09 rdf:first sg:person.01143530261.55
110 rdf:rest N48e3ee77b6e84f9f9712139289f08bb9
111 Ne27d19aed228437796d5fbc9becfd241 rdf:first sg:person.0735150755.29
112 rdf:rest N2f0003fe9e3947429dc8daaede5b40b4
113 Nea61b5cfe66e4c81b0abd57eba6621d2 schema:name Springer Nature - SN SciGraph project
114 rdf:type schema:Organization
115 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
116 schema:name Medical and Health Sciences
117 rdf:type schema:DefinedTerm
118 anzsrc-for:1115 schema:inDefinedTermSet anzsrc-for:
119 schema:name Pharmacology and Pharmaceutical Sciences
120 rdf:type schema:DefinedTerm
121 sg:grant.3859087 http://pending.schema.org/fundedItem sg:pub.10.1038/nature20613
122 rdf:type schema:MonetaryGrant
123 sg:journal.1018957 schema:issn 0090-0028
124 1476-4687
125 schema:name Nature
126 rdf:type schema:Periodical
127 sg:person.01143530261.55 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
128 schema:familyName Shao
129 schema:givenName Zhenhua
130 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01143530261.55
131 rdf:type schema:Person
132 sg:person.01154454461.00 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
133 schema:familyName Rosenbaum
134 schema:givenName Daniel M.
135 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01154454461.00
136 rdf:type schema:Person
137 sg:person.013164203274.32 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
138 schema:familyName Wang
139 schema:givenName Junmei
140 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013164203274.32
141 rdf:type schema:Person
142 sg:person.015627704151.30 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
143 schema:familyName Chapman
144 schema:givenName Karen
145 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015627704151.30
146 rdf:type schema:Person
147 sg:person.016425264551.54 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
148 schema:familyName Grzemska
149 schema:givenName Magdalena
150 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016425264551.54
151 rdf:type schema:Person
152 sg:person.0713053261.91 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
153 schema:familyName Yin
154 schema:givenName Jie
155 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0713053261.91
156 rdf:type schema:Person
157 sg:person.0735150755.29 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
158 schema:familyName Clark
159 schema:givenName Lindsay
160 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0735150755.29
161 rdf:type schema:Person
162 sg:pub.10.1007/s11481-015-9600-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027008353
163 https://doi.org/10.1007/s11481-015-9600-6
164 rdf:type schema:CreativeWork
165 sg:pub.10.1038/nature07063 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013925337
166 https://doi.org/10.1038/nature07063
167 rdf:type schema:CreativeWork
168 sg:pub.10.1038/nm.3265 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037773319
169 https://doi.org/10.1038/nm.3265
170 rdf:type schema:CreativeWork
171 sg:pub.10.1038/nprot.2009.31 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021131005
172 https://doi.org/10.1038/nprot.2009.31
173 rdf:type schema:CreativeWork
174 sg:pub.10.1038/nsmb.3183 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049059057
175 https://doi.org/10.1038/nsmb.3183
176 rdf:type schema:CreativeWork
177 sg:pub.10.1038/srep33302 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033700432
178 https://doi.org/10.1038/srep33302
179 rdf:type schema:CreativeWork
180 https://app.dimensions.ai/details/publication/pub.1079343524 schema:CreativeWork
181 https://doi.org/10.1002/cpt.115 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050064250
182 rdf:type schema:CreativeWork
183 https://doi.org/10.1002/jcc.20290 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012674250
184 rdf:type schema:CreativeWork
185 https://doi.org/10.1016/j.ab.2016.01.016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014374361
186 rdf:type schema:CreativeWork
187 https://doi.org/10.1016/j.cell.2015.04.043 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022061079
188 rdf:type schema:CreativeWork
189 https://doi.org/10.1016/j.cell.2015.06.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007717523
190 rdf:type schema:CreativeWork
191 https://doi.org/10.1016/j.cell.2016.10.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021600730
192 rdf:type schema:CreativeWork
193 https://doi.org/10.1016/j.cmet.2012.07.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031525295
194 rdf:type schema:CreativeWork
195 https://doi.org/10.1016/j.ejphar.2010.10.056 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005261719
196 rdf:type schema:CreativeWork
197 https://doi.org/10.1016/j.neuropharm.2004.07.030 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032240792
198 rdf:type schema:CreativeWork
199 https://doi.org/10.1016/j.nut.2010.11.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047086525
200 rdf:type schema:CreativeWork
201 https://doi.org/10.1016/j.pnpbp.2012.02.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023925597
202 rdf:type schema:CreativeWork
203 https://doi.org/10.1016/s0076-6879(97)76066-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1004907170
204 rdf:type schema:CreativeWork
205 https://doi.org/10.1021/bi060067k schema:sameAs https://app.dimensions.ai/details/publication/pub.1055201672
206 rdf:type schema:CreativeWork
207 https://doi.org/10.1021/bi400842k schema:sameAs https://app.dimensions.ai/details/publication/pub.1028266288
208 rdf:type schema:CreativeWork
209 https://doi.org/10.1021/ja01062a046 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055765175
210 rdf:type schema:CreativeWork
211 https://doi.org/10.1021/jm0306430 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040469800
212 rdf:type schema:CreativeWork
213 https://doi.org/10.1021/jm051256o schema:sameAs https://app.dimensions.ai/details/publication/pub.1055950056
214 rdf:type schema:CreativeWork
215 https://doi.org/10.1021/jm7014974 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055955374
216 rdf:type schema:CreativeWork
217 https://doi.org/10.1038/sj.bjp.0707442 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012111961
218 rdf:type schema:CreativeWork
219 https://doi.org/10.1063/1.1332996 schema:sameAs https://app.dimensions.ai/details/publication/pub.1057695872
220 rdf:type schema:CreativeWork
221 https://doi.org/10.1073/pnas.181342398 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006228920
222 rdf:type schema:CreativeWork
223 https://doi.org/10.1074/jbc.m109.041590 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000837944
224 rdf:type schema:CreativeWork
225 https://doi.org/10.1074/jbc.m111.261651 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035209275
226 rdf:type schema:CreativeWork
227 https://doi.org/10.1074/jbc.m112.390955 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048271405
228 rdf:type schema:CreativeWork
229 https://doi.org/10.1074/jbc.m406648200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007615746
230 rdf:type schema:CreativeWork
231 https://doi.org/10.1074/jbc.m507394200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023750308
232 rdf:type schema:CreativeWork
233 https://doi.org/10.1107/s0021889807021206 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012753217
234 rdf:type schema:CreativeWork
235 https://doi.org/10.1107/s0907444904011679 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027804289
236 rdf:type schema:CreativeWork
237 https://doi.org/10.1107/s0907444904019079 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023777325
238 rdf:type schema:CreativeWork
239 https://doi.org/10.1107/s0907444910007493 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000235100
240 rdf:type schema:CreativeWork
241 https://doi.org/10.1111/febs.12212 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048445470
242 rdf:type schema:CreativeWork
243 https://doi.org/10.1124/jpet.106.118737 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010052209
244 rdf:type schema:CreativeWork
245 https://doi.org/10.1124/jpet.115.230151 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020034616
246 rdf:type schema:CreativeWork
247 https://doi.org/10.1124/mol.105.014407 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003875348
248 rdf:type schema:CreativeWork
249 https://doi.org/10.1124/mol.105.016162 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025529128
250 rdf:type schema:CreativeWork
251 https://doi.org/10.1124/mol.107.034645 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015093363
252 rdf:type schema:CreativeWork
253 https://doi.org/10.1124/mol.62.6.1274 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014605409
254 rdf:type schema:CreativeWork
255 https://doi.org/10.1124/mol.64.3.570 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016016540
256 rdf:type schema:CreativeWork
257 https://doi.org/10.1126/science.1063545 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022454306
258 rdf:type schema:CreativeWork
259 https://doi.org/10.1126/science.1150609 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043965657
260 rdf:type schema:CreativeWork
261 https://doi.org/10.1126/science.1215904 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001612051
262 rdf:type schema:CreativeWork
263 https://doi.org/10.1126/science.289.5480.739 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042667522
264 rdf:type schema:CreativeWork
265 https://doi.org/10.1146/annurev-psych-113011-143739 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026442853
266 rdf:type schema:CreativeWork
267 https://doi.org/10.1517/14728210902736568 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036202237
268 rdf:type schema:CreativeWork
269 https://www.grid.ac/institutes/grid.267313.2 schema:alternateName The University of Texas Southwestern Medical Center
270 schema:name Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
271 Green Center for Systems Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
272 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...