Molecular Architecture of Native HIV-1 gp 120 Trimers

J. Liu, A. Bartesaghi, M. J. Borgnia, G. Sapiro, S. Subramaniam

Research output: Contribution to journalArticlepeer-review

Abstract

A critical step in human and simian immunodeficiency virus (HIV and SIV, respectively) pathogenesis is entry into the target cell. The process of infection is mediated by envelope glycoproteins, Env, which assemble in a trim- eric form on the surface of the virus and bind exposed CD4 molecules on target cells. A monomeric Env is composed of a transmembrane subunit, gp41, and a surface subunit, gpl20. Although there are crystal structures of monomeric Env associated with Fab fragments from the neutralizing antibody bl2 in the CD4 bound and free forms, the structural elucidation of the biologically relevant native trimeric state has been a challenge. In this study, the authors used cryoelectron tomography, in conjunction with the crystallo- graphic information from monomers, to create a model of the trimeric HIV- 1 gpl20 with or without CD4 (Fig. 1). Essentially, the strategy involved fitting of the crystal structure of the monomers into the density of the trimer obtained from cryoelectron tomography. From the ligand-bound and ligand- free molecular models, a schematic of the conformational changes that occur upon CD4 binding was presented (Fig. 1). Briefly, the trimer sticks out of the viral membrane, referred to as the spike, as anchored by gp41 (blue) and with each gpl20 (red) having an exposed CD4 binding site (orange). Upon binding of the ligand, CD4 (yellow), the gpl20 monomers undergo a conformational change to expose the V3 loop, shown as a green patch on Figure le. Such conformational change orients the trimer for proper recognition of a chemokine receptor, as depicted in Figure If.

Original languageEnglish (US)
Pages (from-to)227-228
Number of pages2
JournalChemtracts
Volume21
Issue number6
StatePublished - Jun 2008
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry
  • Molecular Biology

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