3NGB

Crystal structure of broadly and potently neutralizing antibody VRC01 in complex with HIV-1 gp120

Summary for 3NGB

• Entry DOI: 10.2210/pdb3ngb/pdb
• Descriptor: Envelope glycoprotein gp160, Antigen binding fragment of heavy chain: Antibody VRC01, Antigen binding fragment of light chain: Antibody VRC01, ... (9 entities in total)
• Functional Keywords: hiv, gp120, antibody, vrc01, 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: 12
• Total formula weight: 363536.47

Authors

Zhou, T.,Kwong, P.D. (deposition date: 2010-06-11, release date: 2010-07-07, Last modification date: 2024-11-27)

Primary citation

Zhou, T.,Georgiev, I.,Wu, X.,Yang, Z.Y.,Dai, K.,Finzi, A.,Do Kwon, Y.,Scheid, J.F.,Shi, W.,Xu, L.,Yang, Y.,Zhu, J.,Nussenzweig, M.C.,Sodroski, J.,Shapiro, L.,Nabel, G.J.,Mascola, J.R.,Kwong, P.D.
Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01.
Science, 329:811-817, 2010

PubMed Abstract: During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.

PubMed: 20616231
DOI: 10.1126/science.1192819

Experimental method

X-RAY DIFFRACTION (2.68 Å)