+Search query
-Structure paper
Title | Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer. |
---|---|
Journal, issue, pages | Nat Struct Mol Biol, Vol. 24, Issue 4, Page 370-378, Year 2017 |
Publish date | Feb 20, 2017 |
Authors | Qingbo 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 Abstract | 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 ...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 links | Nat Struct Mol Biol / PubMed:28218750 / PubMed Central |
Methods | EM (single particle) |
Resolution | 6.8 Å |
Structure data | 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 |
Source |
|
Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 Entry early intermediate / CD4 binding site / VIRAL PROTEIN-IMMUNE SYSTEM complex |