4XVS

Crystal structure of HIV-1 donor 45 d45-01dG5 coreE gp120 with antibody 45-VRC01.H01+07.O-863513/45-VRC01.L01+07.O-110653 (VRC07_1995)

Summary for 4XVS

• Entry DOI: 10.2210/pdb4xvs/pdb
• Related: 4XVT
• Descriptor: VRC07_1995 45-VRC01.H01+07.O-863513/45-VRC01.L01+07.O-110653 Heavy chain, 45-VRC01.H01+07.O-863513/45-VRC01.L01+07.O-110653 Light chain, Donor 45 01dG5 coreE gp120, ... (5 entities in total)
• Functional Keywords: hiv-1 antibodyomics neutralizing antibody germline binding, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 91531.56

Authors

Joyce, M.G.,Mascola, J.R.,Kwong, P.D. (deposition date: 2015-01-27, release date: 2015-05-06, Last modification date: 2024-10-16)

Primary citation

Wu, X.,Zhang, Z.,Schramm, C.A.,Joyce, M.G.,Do Kwon, Y.,Zhou, T.,Sheng, Z.,Zhang, B.,O'Dell, S.,McKee, K.,Georgiev, I.S.,Chuang, G.Y.,Longo, N.S.,Lynch, R.M.,Saunders, K.O.,Soto, C.,Srivatsan, S.,Yang, Y.,Bailer, R.T.,Louder, M.K.,Mullikin, J.C.,Connors, M.,Kwong, P.D.,Mascola, J.R.,Shapiro, L.
Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection.
Cell, 161:470-485, 2015

PubMed Abstract: HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals, although highly effective antibodies are generally observed only after years of chronic infection. Here, we characterize the rate of maturation and extent of diversity for the lineage that produced the broadly neutralizing antibody VRC01 through longitudinal sampling of peripheral B cell transcripts over 15 years and co-crystal structures of lineage members. Next-generation sequencing identified VRC01-lineage transcripts, which encompassed diverse antibodies organized into distinct phylogenetic clades. Prevalent clades maintained characteristic features of antigen recognition, though each evolved binding loops and disulfides that formed distinct recognition surfaces. Over the course of the study period, VRC01-lineage clades showed continuous evolution, with rates of ∼2 substitutions per 100 nucleotides per year, comparable to that of HIV-1 evolution. This high rate of antibody evolution provides a mechanism by which antibody lineages can achieve extraordinary diversity and, over years of chronic infection, develop effective HIV-1 neutralization.

PubMed: 25865483
DOI: 10.1016/j.cell.2015.03.004

Experimental method

X-RAY DIFFRACTION (1.9 Å)