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

33 Citations (Scopus)

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
StatePublished - Mar 1 2013

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Human immunodeficiency virus 1
HIV-1
glycoproteins
Virus Internalization
Glycoproteins
env Gene Products
viruses
cells

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

The highly conserved layer-3 component of the hiv-1 gp120 inner domain is critical for CD4-required conformational transitions. / Désormeaux, Anik; Coutu, Mathieu; Medjahed, Halima; Pacheco, Beatriz; Herschhorn, Alon; Gu, Christopher; Xiang, Shi-Hua; Mao, Youdong; Sodroski, Joseph; Finzi, Andrés.

In: Journal of virology, Vol. 87, No. 5, 01.03.2013, p. 2549-2562.

Research output: Contribution to journalArticle

Désormeaux, A, Coutu, M, Medjahed, H, Pacheco, B, Herschhorn, A, Gu, C, Xiang, S-H, Mao, Y, Sodroski, J & 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, vol. 87, no. 5, pp. 2549-2562. https://doi.org/10.1128/JVI.03104-12
Désormeaux, Anik ; Coutu, Mathieu ; Medjahed, Halima ; Pacheco, Beatriz ; Herschhorn, Alon ; Gu, Christopher ; Xiang, Shi-Hua ; Mao, Youdong ; Sodroski, Joseph ; Finzi, Andrés. / The highly conserved layer-3 component of the hiv-1 gp120 inner domain is critical for CD4-required conformational transitions. In: Journal of virology. 2013 ; Vol. 87, No. 5. pp. 2549-2562.
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