HIV-1 Env Trimer Opens Through an Asymmetric Intermediate in Which Individual Protomers Adopt Distinct Conformations

Overview

Journal Elife

Specialty Biology

Date 2018 Mar 22

PMID 29561264

Citations 103

Authors

Xiaochu Ma

Maolin Lu

Jason Gorman

Daniel S Terry

Xinyu Hong

Zhou Zhou

Hong Zhao

Roger B Altman

James Arthos

Scott C Blanchard

Peter D Kwong

James B Munro

Walther Mothes

Affiliations

Soon will be listed here.

Abstract

HIV-1 entry into cells requires binding of the viral envelope glycoprotein (Env) to receptor CD4 and coreceptor. Imaging of individual Env molecules on native virions shows Env trimers to be dynamic, spontaneously transitioning between three distinct well-populated conformational states: a pre-triggered Env (State 1), a default intermediate (State 2) and a three-CD4-bound conformation (State 3), which can be stabilized by binding of CD4 and coreceptor-surrogate antibody 17b. Here, using single-molecule Fluorescence Resonance Energy Transfer (smFRET), we show the default intermediate configuration to be asymmetric, with individual protomers adopting distinct conformations. During entry, this asymmetric intermediate forms when a single CD4 molecule engages the trimer. The trimer can then transition to State 3 by binding additional CD4 molecules and coreceptor.

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