4LSS

Crystal structure of broadly and potently neutralizing antibody VRC01 in complex with HIV-1 clade A strain KER_2018_11 gp120

Summary for 4LSS

• Entry DOI: 10.2210/pdb4lss/pdb
• Related: 3NGB 3SE8 3SE9 4J6R 4JB9 4JPV 4JPW
• Descriptor: envelope glycoprotein GP120, HEAVY CHAIN OF ANTIBODY VRC01, LIGHT CHAIN OF ANTIBODY VRC01 with N72T mutation, ... (8 entities in total)
• Functional Keywords: antibody antigen complex, neutralizing antibody vrc01, 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: 90644.45

Authors

Zhou, T.,Moquin, S.,Kwong, P.D. (deposition date: 2013-07-23, release date: 2013-08-21, Last modification date: 2024-10-09)

Primary citation

Zhou, T.,Zhu, J.,Wu, X.,Moquin, S.,Zhang, B.,Acharya, P.,Georgiev, I.S.,Altae-Tran, H.R.,Chuang, G.Y.,Joyce, M.G.,Do Kwon, Y.,Longo, N.S.,Louder, M.K.,Luongo, T.,McKee, K.,Schramm, C.A.,Skinner, J.,Yang, Y.,Yang, Z.,Zhang, Z.,Zheng, A.,Bonsignori, M.,Haynes, B.F.,Scheid, J.F.,Nussenzweig, M.C.,Simek, M.,Burton, D.R.,Koff, W.C.,Mullikin, J.C.,Connors, M.,Shapiro, L.,Nabel, G.J.,Mascola, J.R.,Kwong, P.D.
Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies.
Immunity, 39:245-258, 2013

PubMed Abstract: Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10(12) antibodies make elicitation of specific antibodies uncertain. Here we determine the ontogeny of the VRC01 class by crystallography and next-generation sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120 cocrystal structures reveal VRC01-class recognition to be remarkably similar. B cell transcripts indicate that VRC01-class antibodies require few specific genetic elements, suggesting that naive-B cells with VRC01-class features are generated regularly by recombination. Virtually all of these fail to mature, however, with only a few-likely one-ancestor B cell expanding to form a VRC01-class lineage in each donor. Developmental similarities in multiple donors thus reveal the generation of VRC01-class antibodies to be reproducible in principle, thereby providing a framework for attempts to elicit similar antibodies in the general population.

PubMed: 23911655
DOI: 10.1016/j.immuni.2013.04.012

Experimental method

X-RAY DIFFRACTION (2.59 Å)