HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations. Academic Article uri icon

Overview

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.

publication date

  • March 21, 2018

Research

keywords

  • HIV-1
  • Protein Conformation
  • Protein Multimerization
  • env Gene Products, Human Immunodeficiency Virus

Identity

PubMed Central ID

  • PMC5896952

Scopus Document Identifier

  • 85045694121

Digital Object Identifier (DOI)

  • 10.1021/cb700054k

PubMed ID

  • 29561264

Additional Document Info

volume

  • 7