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TitleQuaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer.
Journal, issue, pagesNat Struct Mol Biol, Vol. 24, Issue 4, Page 370-378, Year 2017
Publish dateFeb 20, 2017
AuthorsQingbo Liu / Priyamvada Acharya / Michael A Dolan / Peng Zhang / Christina Guzzo / Jacky Lu / Alice Kwon / Deepali Gururani / Huiyi Miao / Tatsiana Bylund / Gwo-Yu Chuang / Aliaksandr Druz / Tongqing Zhou / William J Rice / Christoph Wigge / Bridget Carragher / Clinton S Potter / Peter D Kwong / Paolo Lusso /
PubMed AbstractBinding 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 ...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.
External linksNat Struct Mol Biol / PubMed:28218750 / PubMed Central
MethodsEM (single particle)
Resolution6.8 Å
Structure data

8427

5u1f

EMDB-8427: Initial contact of HIV-1 Env with CD4: cryo-EM structure of BG505 DS-SOSIP trimer in complex with CD4 and antibody PGT145
PDB-5u1f: Initial contact of HIV-1 Env with CD4: Cryo-EM structure of BG505 DS-SOSIP trimer in complex with CD4 and antibody PGT145
Method: EM (single particle) / Resolution: 6.8 Å

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 Entry early intermediate / CD4 binding site / VIRAL PROTEIN-IMMUNE SYSTEM complex

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