The β20-β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions

Nat Commun. 2017 Oct 19;8(1):1049. doi: 10.1038/s41467-017-01119-w.


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 types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4 Antigens / metabolism
  • HEK293 Cells
  • HIV Envelope Protein gp120 / chemistry*
  • HIV Envelope Protein gp120 / metabolism
  • HIV-1 / physiology
  • Humans
  • Molecular Probes
  • Protein Binding
  • Protein Conformation
  • Protein Conformation, beta-Strand


  • CD4 Antigens
  • HIV Envelope Protein gp120
  • Molecular Probes
  • gp120 protein, Human immunodeficiency virus 1