8E1P

Crystal structure of BG505 SOSIP.v4.1-GT1.2 trimer in complex with gl-PGV20 and PGT124 Fabs

This is a non-PDB format compatible entry.

Summary for 8E1P

• Entry DOI: 10.2210/pdb8e1p/pdb
• Descriptor: germline PGV20 heavy chain, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (14 entities in total)
• Functional Keywords: hiv envelope glycoprotein, antibody, cd4 antibody, viral protein-immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 18
• Total formula weight: 514276.48

Authors

Sarkar, A.,Kumar, S.,Wilson, I.A. (deposition date: 2022-08-11, release date: 2023-06-21, Last modification date: 2024-11-20)

Primary citation

Caniels, T.G.,Medina-Ramirez, M.,Zhang, J.,Sarkar, A.,Kumar, S.,LaBranche, A.,Derking, R.,Allen, J.D.,Snitselaar, J.L.,Capella-Pujol, J.,Sanchez, I.D.M.,Yasmeen, A.,Diaz, M.,Aldon, Y.,Bijl, T.P.L.,Venkatayogi, S.,Martin Beem, J.S.,Newman, A.,Jiang, C.,Lee, W.H.,Pater, M.,Burger, J.A.,van Breemen, M.J.,de Taeye, S.W.,Rantalainen, K.,LaBranche, C.,Saunders, K.O.,Montefiori, D.,Ozorowski, G.,Ward, A.B.,Crispin, M.,Moore, J.P.,Klasse, P.J.,Haynes, B.F.,Wilson, I.A.,Wiehe, K.,Verkoczy, L.,Sanders, R.W.
Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions.
Cell Rep Med, 4:101003-101003, 2023

PubMed Abstract: Targeting germline (gl-) precursors of broadly neutralizing antibodies (bNAbs) is acknowledged as an important strategy for HIV-1 vaccines. The VRC01-class of bNAbs is attractive because of its distinct genetic signature. However, VRC01-class bNAbs often require extensive somatic hypermutation, including rare insertions and deletions. We describe a BG505 SOSIP trimer, termed GT1.2, to optimize binding to gl-CH31, the unmutated common precursor of the CH30-34 bNAb lineage that acquired a large CDRH1 insertion. The GT1.2 trimer activates gl-CH31 naive B cells in knock-in mice, and B cell responses could be matured by selected boosting immunogens to generate cross-reactive Ab responses. Next-generation B cell sequencing reveals selection for VRC01-class mutations, including insertions in CDRH1 and FWR3 at positions identical to VRC01-class bNAbs, as well as CDRL1 deletions and/or glycine substitutions to accommodate the N276 glycan. These results provide proof of concept for vaccine-induced affinity maturation of B cell lineages that require rare insertions and deletions.

PubMed: 37044090
DOI: 10.1016/j.xcrm.2023.101003

Experimental method

X-RAY DIFFRACTION (3.82 Å)