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

Anik Désormeaux, Mathieu Coutu, Halima Medjahed, Beatriz Pacheco, Alon Herschhorn, Christopher Gu, Shi-Hua Xiang, Youdong Mao, Joseph Sodroski, Andrés Finzi

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2549-2562
Number of pages14
JournalJournal of virology
Volume87
Issue number5
DOIs
Publication statusPublished - Mar 1 2013

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Désormeaux, A., Coutu, M., Medjahed, H., Pacheco, B., Herschhorn, A., Gu, C., ... Finzi, A. (2013). The highly conserved layer-3 component of the hiv-1 gp120 inner domain is critical for CD4-required conformational transitions. Journal of virology, 87(5), 2549-2562. https://doi.org/10.1128/JVI.03104-12