4OCS

Crystal structure of human Fab CAP256-VRC26.10, a potent V1V2-directed HIV-1 neutralizing antibody

Summary for 4OCS

• Entry DOI: 10.2210/pdb4ocs/pdb
• Related: 4OCR 4OCW 4OD1 4OD3 4ODH 4ORG
• Descriptor: CAP256-VRC26.10 light chain, CAP256-VRC26.10 heavy chain (3 entities in total)
• Functional Keywords: fab, hiv-1, v1v2, cap256, vrc26, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 50942.92

Authors

Gorman, J.,Doria-Rose, N.A.,Schramm, C.A.,Moore, P.L.,Mascola, J.R.,Shapiro, L.,Morris, L.,Kwong, P.D. (deposition date: 2014-01-09, release date: 2014-02-26, Last modification date: 2024-10-30)

Primary citation

Doria-Rose, N.A.,Schramm, C.A.,Gorman, J.,Moore, P.L.,Bhiman, J.N.,Dekosky, B.J.,Ernandes, M.J.,Georgiev, I.S.,Kim, H.J.,Pancera, M.,Staupe, R.P.,Altae-Tran, H.R.,Bailer, R.T.,Crooks, E.T.,Cupo, A.,Druz, A.,Garrett, N.J.,Hoi, K.H.,Kong, R.,Louder, M.K.,Longo, N.S.,McKee, K.,Nonyane, M.,O'Dell, S.,Roark, R.S.,Rudicell, R.S.,Schmidt, S.D.,Sheward, D.J.,Soto, C.,Wibmer, C.K.,Yang, Y.,Zhang, Z.,Sequencing, Nisc Comparative,Mullikin, J.C.,Binley, J.M.,Sanders, R.W.,Wilson, I.A.,Moore, J.P.,Ward, A.B.,Georgiou, G.,Williamson, C.,Abdool Karim, S.S.,Morris, L.,Kwong, P.D.,Shapiro, L.,Mascola, J.R.
Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.
Nature, 509:55-62, 2014

PubMed Abstract: Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development.

PubMed: 24590074
DOI: 10.1038/nature13036

Experimental method

X-RAY DIFFRACTION (1.901 Å)