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Core Structure of gp41 from the HIV Envelope Glycoprotein

Chan, David C. and Fass, Deborah and Berger, James M. and Kim, Peter S. (1997) Core Structure of gp41 from the HIV Envelope Glycoprotein. Cell, 89 (2). pp. 263-273. ISSN 0092-8674. https://resolver.caltech.edu/CaltechAUTHORS:20170707-131349087

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Abstract

The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) consists of a complex of gp120 and gp41. gp120 determines viral tropism by binding to target-cell receptors, while gp41 mediates fusion between viral and cellular membranes. Previous studies identified an α-helical domain within gp41 composed of a trimer of two interacting peptides. The crystal structure of this complex, composed of the peptides N36 and C34, is a six-helical bundle. Three N36 helices form an interior, parallel coiled-coil trimer, while three C34 helices pack in an oblique, antiparallel manner into highly conserved, hydrophobic grooves on the surface of this trimer. This structure shows striking similarity to the low-pH-induced conformation of influenza hemagglutinin and likely represents the core of fusion-active gp41. Avenues for the design/discovery of small-molecule inhibitors of HIV infection are directly suggested by this structure.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/S0092-8674(00)80205-6DOIArticle
http://www.sciencedirect.com/science/article/pii/S0092867400802056PublisherArticle
ORCID:
AuthorORCID
Chan, David C.0000-0002-0191-2154
Additional Information:© 1997 Cell Press. Received 3 April 1997, Revised 7 April 1997. We thank the staff, particularly Dr. Craig Ogata, of the Howard Hughes Medical Institute beamline (X4A) at the National Synchrotron Light Source at Brookhaven National Laboratory for invaluable support in collecting MAD data. We are also grateful to Debra Ehrgott and Li Su for help with data collection, Michael Burgess and James Pang for peptide synthesis, and Dr. Steven J. Gamblin for helpful suggestions. D. C. C. is supported by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. J. M. B. is a Whitehead Fellow and acknowledges support from the W. M. Keck Foundation. This work was funded by the Howard Hughes Medical Institute and utilized the W. M. Keck Foundation X-ray Crystallography Facility at the Whitehead Institute.
Funders:
Funding AgencyGrant Number
Jane Coffin Childs Memorial Fund for Medical ResearchUNSPECIFIED
Whitehead Charitable FoundationUNSPECIFIED
W. M. Keck FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:2
Record Number:CaltechAUTHORS:20170707-131349087
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170707-131349087
Official Citation:David C. Chan, Deborah Fass, James M. Berger, Peter S. Kim, Core Structure of gp41 from the HIV Envelope Glycoprotein, Cell, Volume 89, Issue 2, 1997, Pages 263-273, ISSN 0092-8674, http://dx.doi.org/10.1016/S0092-8674(00)80205-6. (http://www.sciencedirect.com/science/article/pii/S0092867400802056)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:78860
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:07 Jul 2017 20:28
Last Modified:24 Feb 2020 10:30

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