5U1F

Initial contact of HIV-1 Env with CD4: Cryo-EM structure of BG505 DS-SOSIP trimer in complex with CD4 and antibody PGT145

Summary for 5U1F

• Entry DOI: 10.2210/pdb5u1f/pdb
• EMDB information: 8427
• Descriptor: BG505 DS-SOSIP gp120, BG505 SOSIP gp41, PGT145 heavy chain, ... (5 entities in total)
• Functional Keywords: hiv-1 entry early intermediate, cd4 binding site, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 9
• Total formula weight: 323692.03

Authors

Acharya, P.,Kwong, P.D.,Potter, C.S.,Carragher, B. (deposition date: 2016-11-28, release date: 2017-02-22, Last modification date: 2018-10-03)

Primary citation

Liu, Q.,Acharya, P.,Dolan, M.A.,Zhang, P.,Guzzo, C.,Lu, J.,Kwon, A.,Gururani, D.,Miao, H.,Bylund, T.,Chuang, G.Y.,Druz, A.,Zhou, T.,Rice, W.J.,Wigge, C.,Carragher, B.,Potter, C.S.,Kwong, P.D.,Lusso, P.
Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer.
Nat. Struct. Mol. Biol., 24:370-378, 2017

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 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.

PubMed: 28218750
DOI: 10.1038/nsmb.3382

Experimental method

ELECTRON MICROSCOPY (6.8 Å)