3SE9

Crystal structure of broadly and potently neutralizing antibody VRC-PG04 in complex with HIV-1 gp120

Summary for 3SE9

• Entry DOI: 10.2210/pdb3se9/pdb
• Related: 3NGB
• Descriptor: HIV-1 Clade AE strain 93TH057 gp120, Heavy chain of antibody VRC-PG04, Light chain of antibody VRC-PG04, ... (10 entities in total)
• Functional Keywords: hiv, gp120, antibody, vrc-pg04, neutralization, vaccine, envelope glycoprotein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 3
• Total formula weight: 90841.22

Authors

Kwong, P.D.,Zhou, T. (deposition date: 2011-06-10, release date: 2011-08-10, Last modification date: 2024-11-27)

Primary citation

Wu, X.,Zhou, T.,Zhu, J.,Zhang, B.,Georgiev, I.,Wang, C.,Chen, X.,Longo, N.S.,Louder, M.,McKee, K.,O'Dell, S.,Perfetto, S.,Schmidt, S.D.,Shi, W.,Wu, L.,Yang, Y.,Yang, Z.Y.,Yang, Z.,Zhang, Z.,Bonsignori, M.,Crump, J.A.,Kapiga, S.H.,Sam, N.E.,Haynes, B.F.,Simek, M.,Burton, D.R.,Koff, W.C.,Doria-Rose, N.A.,Connors, M.,Mullikin, J.C.,Nabel, G.J.,Roederer, M.,Shapiro, L.,Kwong, P.D.,Mascola, J.R.
Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing.
Science, 333:1593-1602, 2011

PubMed Abstract: Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.

PubMed: 21835983
DOI: 10.1126/science.1207532

Experimental method

X-RAY DIFFRACTION (2 Å)