Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer

Nat Struct Mol Biol. 2012 Sep;19(9):893-9. doi: 10.1038/nsmb.2351. Epub 2012 Aug 5.

Abstract

The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike is a molecular machine that mediates virus entry into host cells and is the sole target for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric glycoprotein precursor, gp160, into three gp120 and three gp41 subunits. Here, we describe an ~11-Å cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and three gp41 subunits form a cage-like structure with an interior void surrounding the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane region, the torus-like gp41 ectodomain and a trimer-association domain of gp120 composed of the V1, V2 and V3 variable regions. The cage-like architecture, which is unique among characterized viral envelope proteins, restricts antibody access, reflecting requirements imposed by HIV-1 persistence in the host.

Publication types

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

MeSH terms

  • Cell Line
  • Cryoelectron Microscopy
  • HIV Envelope Protein gp120 / chemistry*
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp160 / metabolism
  • HIV Envelope Protein gp41 / chemistry*
  • HIV Envelope Protein gp41 / metabolism
  • HIV Infections / virology*
  • HIV-1 / chemistry*
  • HIV-1 / metabolism
  • Humans
  • Models, Molecular
  • Protein Conformation
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism

Substances

  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp160
  • HIV Envelope Protein gp41
  • Protein Subunits