Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-03-30

AUTHORS

Jun Lan, Jiwan Ge, Jinfang Yu, Sisi Shan, Huan Zhou, Shilong Fan, Qi Zhang, Xuanling Shi, Qisheng Wang, Linqi Zhang, Xinquan Wang

ABSTRACT

A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1–3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1–3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies. More... »

PAGES

215-220

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41586-020-2180-5

DOI

http://dx.doi.org/10.1038/s41586-020-2180-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1125975734

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32225176


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34 schema:description A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1–3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1–3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.
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42 ACE2 binding
43 ACE2 receptor
44 China
45 Hubei Province
46 Province
47 SARS
48 SARS CoV receptor-binding domain
49 SARS-CoV antibody
50 SARS-CoV-2
51 SARS-CoV-2 receptor-binding domain
52 SARS-CoV-2 spike receptor-binding domain
53 Wuhan city
54 analysis
55 antibodies
56 atomic level
57 binding
58 chain properties
59 city
60 convergent evolution
61 coronavirus
62 countries
63 cross-reactive antibodies
64 crystal structure
65 domain
66 epitopes
67 evolution
68 future identification
69 identification
70 infection
71 initial step
72 insights
73 levels
74 majority
75 mode
76 outbreak
77 pathogenic coronaviruses
78 properties
79 protein
80 receptor ACE2
81 receptor-binding domain
82 receptor4
83 receptors
84 residues
85 sequence
86 side-chain properties
87 similarity
88 spike protein
89 spike receptor-binding domain
90 step
91 structural analysis
92 structure
93 such similarities
94 world1–3
95 schema:name Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor
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