4FQ1

Crystal Structure of PGT121 Fab

Summary for 4FQ1

• Entry DOI: 10.2210/pdb4fq1/pdb
• Related: 4FQ2 4FQC 4FQQ
• Descriptor: Fab heavy chain, Fab light chain, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: ig fold, anti hiv, antibody, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 49167.65

Authors

Scharf, L.,Bjorkman, P.J. (deposition date: 2012-06-24, release date: 2012-11-14, Last modification date: 2021-05-19)

Primary citation

Mouquet, H.,Scharf, L.,Euler, Z.,Liu, Y.,Eden, C.,Scheid, J.F.,Halper-Stromberg, A.,Gnanapragasam, P.N.,Spencer, D.I.,Seaman, M.S.,Schuitemaker, H.,Feizi, T.,Nussenzweig, M.C.,Bjorkman, P.J.
Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies.
Proc.Natl.Acad.Sci.USA, 109:E3268-E3277, 2012

PubMed Abstract: Broadly neutralizing HIV antibodies (bNAbs) can recognize carbohydrate-dependent epitopes on gp120. In contrast to previously characterized glycan-dependent bNAbs that recognize high-mannose N-glycans, PGT121 binds complex-type N-glycans in glycan microarrays. We isolated the B-cell clone encoding PGT121, which segregates into PGT121-like and 10-1074-like groups distinguished by sequence, binding affinity, carbohydrate recognition, and neutralizing activity. Group 10-1074 exhibits remarkable potency and breadth but no detectable binding to protein-free glycans. Crystal structures of unliganded PGT121, 10-1074, and their likely germ-line precursor reveal that differential carbohydrate recognition maps to a cleft between complementarity determining region (CDR)H2 and CDRH3. This cleft was occupied by a complex-type N-glycan in a "liganded" PGT121 structure. Swapping glycan contact residues between PGT121 and 10-1074 confirmed their importance for neutralization. Although PGT121 binds complex-type N-glycans, PGT121 recognized high-mannose-only HIV envelopes in isolation and on virions. As HIV envelopes exhibit varying proportions of high-mannose- and complex-type N-glycans, these results suggest promiscuous carbohydrate interactions, an advantageous adaptation ensuring neutralization of all viruses within a given strain.

PubMed: 23115339
DOI: 10.1073/pnas.1217207109

Experimental method

X-RAY DIFFRACTION (3 Å)