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Volume 6 Supplement 3

AIDS Vaccine 2009

  • Poster presentation
  • Open Access

P09-13. Structure of HIV-1 gp41 interactive region: layered architecture and basis of conformational mobility

  • M Pancera1,
  • S Majeed1,
  • Y Ban2,
  • L Chen1,
  • C Huang1,
  • L Kong1,
  • Y Kwon1,
  • J Stuckey1,
  • T Zhou1,
  • J Robinson3,
  • W Schief2,
  • J Sodroski4,
  • R Wyatt1 and
  • P Kwong1
Retrovirology20096(Suppl 3):P126

Published: 22 October 2009


Host Immune ResponseImmune EvasionSequence SegmentLayered ArchitectureConformational Rearrangement


Crystal structures of unliganded, CD4-bound, and antibody-bound gp120 core show large conformational rearrangements upon ligand binding. Moreover, cryo-EM tomograms of the HIV-1 viral spike (gp120/gp41) also show large ligand-induced shifts in gp120 orientation. Conformational change is one mechanism that HIV-1 has developed to evade the host immune response. We hypothesized that the key to understanding this mobility resided in the critical gp41-interactive region of gp120. However, previously determined core structures all contained deletions of the gp41-interactive region.


We determined the structure at 3 Å resolution for an HXBc2 gp120 core with intact gp41-interactive region, bound to two-domain CD4, and the antigen-binding fragment of 48 d.


The new structure revealed that most of the N terminus packs intimately against the previously determined core, adding three β-strands and one α-helix to the inner domain. The tips of the newly defined termini form two anti-parallel β-strands, which extend away from gp120. Meanwhile, the gp41-interactive region consists of a single surface composed of at least four different sequence segments, and includes the N and C tips and a central seven-stranded β-sandwich. The more complete inner domain is centered about this seven-stranded β-sandwich, from which three structural excursions emanate. Each of these excursions packs as a separate topological layer. Comparison to other gp120 structures indicates that these layers are structurally plastic with weak interlayer interactions.


Structural analysis and cryo-EM tomograms were consistent with a model in which the layers in the inner domain of gp120 act as a shape-changing spacer between structurally invariant outer domain and gp41-associated β-sandwich to allow movement within the viral spike. Thus, we define a layered gp120 architecture that allows for extraordinary conformational change while retaining gp41 interaction through an invariant β-sandwich and associated termini. The mechanism of gp120 mobility revealed here assists HIV-1 in both immune evasion and entry.

Authors’ Affiliations

University of Washington, Seattle, USA
Department of Pediatrics, Tulane University Medical Center, New Orleans, USA
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, USA


© Pancera et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.