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Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer.

Publication ,  Journal Article
Liu, Q; Acharya, P; Dolan, MA; Zhang, P; Guzzo, C; Lu, J; Kwon, A; Gururani, D; Miao, H; Bylund, T; Chuang, G-Y; Druz, A; Zhou, T; Rice, WJ ...
Published in: Nat Struct Mol Biol
April 2017

Binding of the gp120 envelope (Env) glycoprotein to the CD4 receptor is the first step in the HIV-1 infectious cycle. Although the CD4-binding site has been extensively characterized, the initial receptor interaction has been difficult to study because of major CD4-induced structural rearrangements. Here we used cryogenic electron microscopy (cryo-EM) to visualize the initial contact of CD4 with the HIV-1 Env trimer at 6.8-Å resolution. A single CD4 molecule is embraced by a quaternary HIV-1-Env surface formed by coalescence of the previously defined CD4-contact region with a second CD4-binding site (CD4-BS2) in the inner domain of a neighboring gp120 protomer. Disruption of CD4-BS2 destabilized CD4-trimer interaction and abrogated HIV-1 infectivity by preventing the acquisition of coreceptor-binding competence. A corresponding reduction in HIV-1 infectivity occurred after the mutation of CD4 residues that interact with CD4-BS2. Our results document the critical role of quaternary interactions in the initial HIV-Env-receptor contact, with implications for treatment and vaccine design.

Duke Scholars

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Published In

Nat Struct Mol Biol

DOI

EISSN

1545-9985

Publication Date

April 2017

Volume

24

Issue

4

Start / End Page

370 / 378

Location

United States

Related Subject Headings

  • Surface Plasmon Resonance
  • Protein Structure, Quaternary
  • Protein Stability
  • Protein Multimerization
  • Protein Binding
  • Mutagenesis
  • Kinetics
  • Humans
  • HIV-1
  • HIV Infections
 

Citation

APA
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ICMJE
MLA
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Liu, Q., Acharya, P., Dolan, M. A., Zhang, P., Guzzo, C., Lu, J., … Lusso, P. (2017). Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer. Nat Struct Mol Biol, 24(4), 370–378. https://doi.org/10.1038/nsmb.3382
Liu, Qingbo, Priyamvada Acharya, Michael A. Dolan, Peng Zhang, Christina Guzzo, Jacky Lu, Alice Kwon, et al. “Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer.Nat Struct Mol Biol 24, no. 4 (April 2017): 370–78. https://doi.org/10.1038/nsmb.3382.
Liu Q, Acharya P, Dolan MA, Zhang P, Guzzo C, Lu J, et al. Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer. Nat Struct Mol Biol. 2017 Apr;24(4):370–8.
Liu, Qingbo, et al. “Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer.Nat Struct Mol Biol, vol. 24, no. 4, Apr. 2017, pp. 370–78. Pubmed, doi:10.1038/nsmb.3382.
Liu Q, Acharya P, Dolan MA, Zhang P, Guzzo C, Lu J, Kwon A, Gururani D, Miao H, Bylund T, Chuang G-Y, Druz A, Zhou T, Rice WJ, Wigge C, Carragher B, Potter CS, Kwong PD, Lusso P. Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer. Nat Struct Mol Biol. 2017 Apr;24(4):370–378.

Published In

Nat Struct Mol Biol

DOI

EISSN

1545-9985

Publication Date

April 2017

Volume

24

Issue

4

Start / End Page

370 / 378

Location

United States

Related Subject Headings

  • Surface Plasmon Resonance
  • Protein Structure, Quaternary
  • Protein Stability
  • Protein Multimerization
  • Protein Binding
  • Mutagenesis
  • Kinetics
  • Humans
  • HIV-1
  • HIV Infections