6B3D

Crystal structure of anti-HIV antibody PGT128 in complex with a bacterially derived synthetic mimetic of Man9.

6B3D の概要

• エントリーDOI: 10.2210/pdb6b3d/pdb
• 分子名称: PGT128 Fab light chain, PGT128 Fab heavy chain, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose, ... (8 entities in total)
• 機能のキーワード: antibody, glycan, mannose, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50006.56

構造登録者

Murrell, S.,Wilson, I.A. (登録日: 2017-09-21, 公開日: 2017-12-06, 最終更新日: 2024-10-23)

主引用文献

Pantophlet, R.,Trattnig, N.,Murrell, S.,Lu, N.,Chau, D.,Rempel, C.,Wilson, I.A.,Kosma, P.
Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity.
Nat Commun, 8:1601-1601, 2017

PubMed Abstract: Oligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system. One of these mimetics is bound avidly by members of a family of oligomannose-specific bnAbs and their putative common germline precursor when presented as a glycoconjugate. The crystal structure of one of the mimetics bound to a member of this bnAb family confirms the antigenic resemblance. Lastly, immunization of human-antibody transgenic animals with a lead mimetic evokes nAbs with specificities approaching those of existing bnAbs. These results provide evidence for utilizing antigenic mimicry to elicit oligomannose-specific bnAbs to HIV-1.

PubMed: 29150603
DOI: 10.1038/s41467-017-01640-y

実験手法

X-RAY DIFFRACTION (2.271 Å)