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J Virol. 2013 Mar;87(5):2549-62. doi: 10.1128/JVI.03104-12. Epub 2012 Dec 19.

The highly conserved layer-3 component of the HIV-1 gp120 inner domain is critical for CD4-required conformational transitions.

Author information

1
Centre de Recherche du CHUM, Université de Montréal, Montreal, Quebec, Canada.

Abstract

The trimeric envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) mediates virus entry into host cells. CD4 engagement with the gp120 exterior envelope glycoprotein subunit represents the first step during HIV-1 entry. CD4-induced conformational changes in the gp120 inner domain involve three potentially flexible topological layers (layers 1, 2, and 3). Structural rearrangements between layer 1 and layer 2 have been shown to facilitate the transition of the envelope glycoprotein trimer from the unliganded to the CD4-bound state and to stabilize gp120-CD4 interaction. However, our understanding of CD4-induced conformational changes in the gp120 inner domain remains incomplete. Here, we report that a highly conserved element of the gp120 inner domain, layer 3, plays a pivot-like role in these allosteric changes. In the unliganded state, layer 3 modulates the association of gp120 with the Env trimer, probably by influencing the relationship of the gp120 inner and outer domains. Importantly, layer 3 governs the efficiency of the initial gp120 interaction with CD4, a function that can also be fulfilled by filling the Phe43 cavity. This work defines the functional importance of layer 3 and completes a picture detailing the role of the gp120 inner domain in CD4-induced conformational transitions in the HIV-1 Env trimer.

PMID:
23255784
PMCID:
PMC3571356
DOI:
10.1128/JVI.03104-12
[Indexed for MEDLINE]
Free PMC Article

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