CD4-induced activation in a soluble HIV-1 Env trimer Academic Article uri icon

Overview

MeSH Major

  • Antigens, CD4
  • Protein Multimerization
  • Protein Structure, Quaternary
  • env Gene Products, Human Immunodeficiency Virus

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.

publication date

  • July 8, 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4231881

Digital Object Identifier (DOI)

  • 10.1016/j.str.2014.05.001

PubMed ID

  • 24931470

Additional Document Info

start page

  • 974

end page

  • 84

volume

  • 22

number

  • 7