CD4-induced activation in a soluble HIV-1 Env trimer.

TitleCD4-induced activation in a soluble HIV-1 Env trimer.
Publication TypeJournal Article
Year of Publication2014
AuthorsGuttman M, Garcia NK, Cupo A, Matsui T, Julien J-P, Sanders RW, Wilson IA, Moore JP, Lee KK
JournalStructure
Volume22
Issue7
Pagination974-84
Date Published07/08/2014
ISSN1878-4186
Abstract

The HIV envelope glycoprotein (Env) trimer undergoes receptor-induced conformational changes that drive fusion of the viral and cellular membranes. Env conformational changes have been observed using low-resolution electron microscopy, but only large-scale rearrangements have been visible. Here, we use hydrogen-deuterium exchange and oxidative labeling to gain a more precise understanding of the unliganded and CD4-bound forms of soluble Env trimers (SOSIP.664), including their glycan composition. CD4 activation induces the reorganization of bridging sheet elements, V1/V2 and V3, much of the gp120 inner domain, and the gp41 fusion subunit. Two CD4 binding site-targeted inhibitors have substantially different effects: NBD-556 partially mimics CD4-induced destabilization of the V1/V2 and V3 crown, whereas BMS-806 only affects regions around the gp120/gp41 interface. The structural information presented here increases our knowledge of CD4- and small molecule-induced conformational changes in Env and the allosteric pathways that lead to membrane fusion.

DOI10.1016/j.str.2014.05.001
Alternate JournalStructure
PubMed ID24931470
Grant ListF32-GM097805 / GM / NIGMS NIH HHS / United States
P01-AI82362 / AI / NIAID NIH HHS / United States
P30-AI027767 / AI / NIAID NIH HHS / United States
P41-GM103393 / GM / NIGMS NIH HHS / United States
P41-RR001209 / RR / NCRR NIH HHS / United States
R00 GM080352 / GM / NIGMS NIH HHS / United States
R00-GM080352 / GM / NIGMS NIH HHS / United States
R01 GM099989 / GM / NIGMS NIH HHS / United States
R01-AI084817 / AI / NIAID NIH HHS / United States
R01-AI41420 / AI / NIAID NIH HHS / United States
R01-GM099989 / GM / NIGMS NIH HHS / United States
R37-AI36082 / AI / NIAID NIH HHS / United States
T32-GM007750 / GM / NIGMS NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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