6MTT

Crystal structure of VRC46.01 Fab in complex with gp41 peptide

Summary for 6MTT

• Entry DOI: 10.2210/pdb6mtt/pdb
• Descriptor: Antibody VRC46.01 Fb light chain, Antibody VRC46.01 Fab heavy chain, RV217 founder virus gp41 peptide, ... (4 entities in total)
• Functional Keywords: anti-hiv-1 human antibody, mper, gp41, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 51001.12

Authors

Kwon, Y.D.,Druz, A.,Law, W.H.,Peng, D.,Veradi, R.,Doria-Rose, N.A.,Kwong, P.D. (deposition date: 2018-10-21, release date: 2019-03-27, Last modification date: 2024-10-23)

Primary citation

Krebs, S.J.,Kwon, Y.D.,Schramm, C.A.,Law, W.H.,Donofrio, G.,Zhou, K.H.,Gift, S.,Dussupt, V.,Georgiev, I.S.,Schatzle, S.,McDaniel, J.R.,Lai, Y.T.,Sastry, M.,Zhang, B.,Jarosinski, M.C.,Ransier, A.,Chenine, A.L.,Asokan, M.,Bailer, R.T.,Bose, M.,Cagigi, A.,Cale, E.M.,Chuang, G.Y.,Darko, S.,Driscoll, J.I.,Druz, A.,Gorman, J.,Laboune, F.,Louder, M.K.,McKee, K.,Mendez, L.,Moody, M.A.,O'Sullivan, A.M.,Owen, C.,Peng, D.,Rawi, R.,Sanders-Buell, E.,Shen, C.H.,Shiakolas, A.R.,Stephens, T.,Tsybovsky, Y.,Tucker, C.,Verardi, R.,Wang, K.,Zhou, J.,Zhou, T.,Georgiou, G.,Alam, S.M.,Haynes, B.F.,Rolland, M.,Matyas, G.R.,Polonis, V.R.,McDermott, A.B.,Douek, D.C.,Shapiro, L.,Tovanabutra, S.,Michael, N.L.,Mascola, J.R.,Robb, M.L.,Kwong, P.D.,Doria-Rose, N.A.
Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.
Immunity, 50:677-691.e13, 2019

PubMed Abstract: Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design.

PubMed: 30876875
DOI: 10.1016/j.immuni.2019.02.008

Experimental method

X-RAY DIFFRACTION (1.7 Å)