Structural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers.

TitleStructural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers.
Publication TypeJournal Article
Year of Publication2014
AuthorsBlattner C, Lee J H, Sliepen K, Derking R, Falkowska E, de la Peña ATorrents, Cupo A, Julien J-P, van Gils M, Lee PS, Peng W, Paulson JC, Poignard P, Burton DR, Moore JP, Sanders RW, Wilson IA, Ward AB
JournalImmunity
Volume40
Issue5
Pagination669-80
Date Published05/15/2014
ISSN1097-4180
Abstract

All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer.

DOI10.1016/j.immuni.2014.04.008
Alternate JournalImmunity
PubMed ID24768348
Grant ListP01 AI082362 / AI / NIAID NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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