5T4Z

STRUCTURE OF THE ANTI-HIV ANTIBODY DH501 THAT BINDS GP120 V3 GLYCAN AND THE BASE OF V3 WITH FREE MAN9 GLYCAN

Summary for 5T4Z

• Entry DOI: 10.2210/pdb5t4z/pdb
• Related: 5IIE
• Descriptor: antibody DH501 Fab heavy chain, antibody DH501 Fab light chain, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose, ... (5 entities in total)
• Functional Keywords: hiv-1 antibody gp120, immune system
• Biological source: Macaca mulatta (Rhesus monkey); More
• Total number of polymer chains: 4
• Total formula weight: 95582.76

Authors

Nicely, N.I.,Haynes, B.F. (deposition date: 2016-08-30, release date: 2017-03-08, Last modification date: 2024-11-06)

Primary citation

Saunders, K.O.,Nicely, N.I.,Wiehe, K.,Bonsignori, M.,Meyerhoff, R.R.,Parks, R.,Walkowicz, W.E.,Aussedat, B.,Wu, N.R.,Cai, F.,Vohra, Y.,Park, P.K.,Eaton, A.,Go, E.P.,Sutherland, L.L.,Scearce, R.M.,Barouch, D.H.,Zhang, R.,Von Holle, T.,Overman, R.G.,Anasti, K.,Sanders, R.W.,Moody, M.A.,Kepler, T.B.,Korber, B.,Desaire, H.,Santra, S.,Letvin, N.L.,Nabel, G.J.,Montefiori, D.C.,Tomaras, G.D.,Liao, H.X.,Alam, S.M.,Danishefsky, S.J.,Haynes, B.F.
Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates.
Cell Rep, 18:2175-2188, 2017

PubMed Abstract: Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans-a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors.

PubMed: 28249163
DOI: 10.1016/j.celrep.2017.02.003

Experimental method

X-RAY DIFFRACTION (1.991 Å)