4RWY

Crystal structure of VH1-46 germline-derived CD4-binding site-directed antibody 8ANC131 in complex with HIV-1 clade B YU2 gp120

Summary for 4RWY

• Entry DOI: 10.2210/pdb4rwy/pdb
• Related: 4RX4
• Descriptor: HIV-1 YU2 gp120, Antibody 8ANC131 Heavy chain, Antibody 8ANC131 Light chain, ... (8 entities in total)
• Functional Keywords: hiv-1 attachment protein, broadly neutralizing antibody 8anc131, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 3
• Total formula weight: 91349.86

Authors

Acharya, P.,Luongo, T.S.,Kwong, P.D. (deposition date: 2014-12-08, release date: 2015-07-01, Last modification date: 2024-10-16)

Primary citation

Zhou, T.,Lynch, R.M.,Chen, L.,Acharya, P.,Wu, X.,Doria-Rose, N.A.,Joyce, M.G.,Lingwood, D.,Soto, C.,Bailer, R.T.,Ernandes, M.J.,Kong, R.,Longo, N.S.,Louder, M.K.,McKee, K.,O'Dell, S.,Schmidt, S.D.,Tran, L.,Yang, Z.,Druz, A.,Luongo, T.S.,Moquin, S.,Srivatsan, S.,Yang, Y.,Zhang, B.,Zheng, A.,Pancera, M.,Kirys, T.,Georgiev, I.S.,Gindin, T.,Peng, H.P.,Yang, A.S.,Mullikin, J.C.,Gray, M.D.,Stamatatos, L.,Burton, D.R.,Koff, W.C.,Cohen, M.S.,Haynes, B.F.,Casazza, J.P.,Connors, M.,Corti, D.,Lanzavecchia, A.,Sattentau, Q.J.,Weiss, R.A.,West, A.P.,Bjorkman, P.J.,Scheid, J.F.,Nussenzweig, M.C.,Shapiro, L.,Mascola, J.R.,Kwong, P.D.
Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors.
Cell(Cambridge,Mass.), 161:1280-1292, 2015

PubMed Abstract: The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated CD4-binding-site (CD4bs) antibodies and analyzed 16 co-crystal structures -8 determined here- of CD4bs antibodies from 14 donors. The 16 antibodies segregated by recognition mode and developmental ontogeny into two types: CDR H3-dominated and VH-gene-restricted. Both could achieve greater than 80% neutralization breadth, and both could develop in the same donor. Although paratope chemistries differed, all 16 gp120-CD4bs antibody complexes showed geometric similarity, with antibody-neutralization breadth correlating with antibody-angle of approach relative to the most effective antibody of each type. The repertoire for effective recognition of the CD4 supersite thus comprises antibodies with distinct paratopes arrayed about two optimal geometric orientations, one achieved by CDR H3 ontogenies and the other achieved by VH-gene-restricted ontogenies.

PubMed: 26004070
DOI: 10.1016/j.cell.2015.05.007

Experimental method

X-RAY DIFFRACTION (2.128 Å)