4FQC

Crystal Structure of PGT121 Fab Bound to a complex-type sialylated N-glycan

4FQC の概要

• エントリーDOI: 10.2210/pdb4fqc/pdb
• 関連するPDBエントリー: 4FQ1 4FQ2 4FQQ
• 分子名称: Fab heavy chain, Fab light chain, N-acetyl-alpha-neuraminic acid-(2-6)-beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: ig fold, anti hiv, antibody, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51026.40

構造登録者

Scharf, L.,Bjorkman, P.J. (登録日: 2012-06-25, 公開日: 2012-11-14, 最終更新日: 2024-11-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)