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Volume 6 Supplement 3

AIDS Vaccine 2009

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


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.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Pancera, M., Majeed, S., Ban, Y. et al. P09-13. Structure of HIV-1 gp41 interactive region: layered architecture and basis of conformational mobility. Retrovirology 6 (Suppl 3), P126 (2009).

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