Distribution and three-dimensional structure of AIDS virus envelope spikes

Nature. 2006 Jun 15;441(7095):847-52. doi: 10.1038/nature04817. Epub 2006 May 24.

Abstract

Envelope glycoprotein (Env) spikes on AIDS retroviruses initiate infection of host cells and are therefore targets for vaccine development. Though crystal structures for partial Env subunits are known, the structure and distribution of native Env spikes on virions is obscure. We applied cryoelectron microscopy tomography to define ultrastructural details of spikes. Virions of wild-type human immunodeficiency virus 1 (HIV-1) and a mutant simian immunodeficiency virus (SIV) had approximately 14 and approximately 73 spikes per particle, respectively, with some clustering of HIV-1 spikes. Three-dimensional averaging showed that the surface glycoprotein (gp120) 'head' of each subunit of the trimeric SIV spike contains a primary mass, with two secondary lobes. The transmembrane glycoprotein 'stalk' of each trimer is composed of three independent legs that project obliquely from the trimer head, tripod-like. Reconciling available atomic structures with the three-dimensional whole spike density map yields insights into the orientation of Env spike structural elements and possible structural bases of their functions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acquired Immunodeficiency Syndrome / virology
  • Cryoelectron Microscopy
  • Glycoproteins / chemistry
  • Glycoproteins / ultrastructure
  • HIV Envelope Protein gp120 / chemistry*
  • HIV Envelope Protein gp120 / ultrastructure*
  • HIV-1 / chemistry*
  • HIV-1 / genetics
  • HIV-1 / ultrastructure*
  • Ligands
  • Models, Molecular
  • Protein Structure, Quaternary
  • Protein Subunits / chemistry
  • Simian Immunodeficiency Virus / chemistry
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / ultrastructure
  • Structure-Activity Relationship
  • Tomography

Substances

  • Glycoproteins
  • HIV Envelope Protein gp120
  • Ligands
  • Protein Subunits