Evolutionary balance between foldability and functionality of a glucose transporter View Full Text


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Article Info

DATE

2022-04-28

AUTHORS

Hyun-Kyu Choi, Hyunook Kang, Chanwoo Lee, Hyun Gyu Kim, Ben P. Phillips, Soohyung Park, Charlotte Tumescheit, Sang Ah Kim, Hansol Lee, Soung-Hun Roh, Heedeok Hong, Martin Steinegger, Wonpil Im, Elizabeth A. Miller, Hee-Jung Choi, Tae-Young Yoon

ABSTRACT

Despite advances in resolving the structures of multi-pass membrane proteins, little is known about the native folding pathways of these complex structures. Using single-molecule magnetic tweezers, we here report a folding pathway of purified human glucose transporter 3 (GLUT3) reconstituted within synthetic lipid bilayers. The N-terminal major facilitator superfamily (MFS) fold strictly forms first, serving as a structural template for its C-terminal counterpart. We found polar residues comprising the conduit for glucose molecules present major folding challenges. The endoplasmic reticulum membrane protein complex facilitates insertion of these hydrophilic transmembrane helices, thrusting GLUT3’s microstate sampling toward folded structures. Final assembly between the N- and C-terminal MFS folds depends on specific lipids that ease desolvation of the lipid shells surrounding the domain interfaces. Sequence analysis suggests that this asymmetric folding propensity across the N- and C-terminal MFS folds prevails for metazoan sugar porters, revealing evolutionary conflicts between foldability and functionality faced by many multi-pass membrane proteins. More... »

PAGES

713-723

References to SciGraph publications

  • 2018-03-26. Unfolding of a ClC chloride transporter retains memory of its evolutionary history in NATURE CHEMICAL BIOLOGY
  • 2020-08-19. An intramembrane chaperone complex facilitates membrane protein biogenesis in NATURE
  • 2015-07-15. Molecular basis of ligand recognition and transport by glucose transporters in NATURE
  • 2007-12. Molecular code for transmembrane-helix recognition by the Sec61 translocon in NATURE
  • 2011-12-25. HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment in NATURE METHODS
  • 2018-09-07. Focused clamping of a single neuronal SNARE complex by complexin under high mechanical tension in NATURE COMMUNICATIONS
  • 2003-11-18. The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins in PFLÜGERS ARCHIV - EUROPEAN JOURNAL OF PHYSIOLOGY
  • 2019-09-14. HH-suite3 for fast remote homology detection and deep protein annotation in BMC BIOINFORMATICS
  • 2021-09-23. The mechanisms of integral membrane protein biogenesis in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2018-09-27. Thiol-Redox Proteomics to Study Reversible Protein Thiol Oxidations in Bacteria in MICROBIAL PROTEOMICS
  • 2016-09-05. YidC assists the stepwise and stochastic folding of membrane proteins in NATURE CHEMICAL BIOLOGY
  • 2005-11-30. Solving the membrane protein folding problem in NATURE
  • 2014-07-20. The Get1/2 transmembrane complex is an endoplasmic-reticulum membrane protein insertase in NATURE
  • 2016-01-13. Understanding transport by the major facilitator superfamily (MFS): structures pave the way in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2015-10-19. Mapping the energy landscape for second-stage folding of a single membrane protein in NATURE CHEMICAL BIOLOGY
  • 2017-10-12. The folding, stability and function of lactose permease differ in their dependence on bilayer lipid composition in SCIENTIFIC REPORTS
  • 2009-08-13. Mapping the human membrane proteome: a majority of the human membrane proteins can be classified according to function and evolutionary origin in BMC BIOLOGY
  • 2014-11-25. GLUT2, glucose sensing and glucose homeostasis in DIABETOLOGIA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41589-022-01002-w

    DOI

    http://dx.doi.org/10.1038/s41589-022-01002-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1147397557

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35484435


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