The β20-β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions. Academic Article uri icon

Overview

abstract

  • The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally "closed" State 1 to more "open" conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control switch for Env structural rearrangements. We identify the gp120 β20-β21 element as a major regulator of Env transitions. Several amino acid changes in the β20-β21 base lead to open Env conformations, recapitulating the structural changes induced by CD4 binding. These HIV-1 mutants require less CD4 to infect cells and are relatively resistant to State 1-preferring broadly neutralizing antibodies. These data provide insights into the molecular mechanism and vulnerability of HIV-1 entry.

publication date

  • October 19, 2017

Research

keywords

  • HIV Envelope Protein gp120

Identity

PubMed Central ID

  • PMC5648922

Scopus Document Identifier

  • 85031943201

Digital Object Identifier (DOI)

  • 10.1002/jcc.20084

PubMed ID

  • 29051495

Additional Document Info

volume

  • 8

issue

  • 1