4YDK

Crystal structure of broadly and potently neutralizing antibody C38-VRC16.01 in complex with HIV-1 clade AE strain 93TH057 gp120

Summary for 4YDK

• Entry DOI: 10.2210/pdb4ydk/pdb
• Related: 4YDI 4YDJ 4YDL
• Descriptor: Envelope glycoprotein gp160,Envelope glycoprotein gp160, HEAVY CHAIN OF ANTIBODY C38-VRC16.01, LIGHT CHAIN OF ANTIBODY C38-VRC16.01, ... (8 entities in total)
• Functional Keywords: antibody, hiv-1, immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 3
• Total formula weight: 92270.04

Authors

Zhou, T.,Moquin, S.,Zheng, A.,Kwong, P.D. (deposition date: 2015-02-22, release date: 2015-06-03, 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, 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 (2.051 Å)