9MR7

Genetiocally detoxified pertussis toxin in complex with hu1B7 Fab and hu11E6 Fab

これはPDB形式変換不可エントリーです。

9MR7 の概要

• エントリーDOI: 10.2210/pdb9mr7/pdb
• EMDBエントリー: 48554
• 分子名称: Pertussis toxin subunit 1, Pertussis toxin subunit 2, Pertussis toxin subunit 3, ... (9 entities in total)
• 機能のキーワード: toxin, pertussis, antibody
• 由来する生物種: Bordetella pertussis; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 248366.46

構造登録者

Goldsmith, J.A.,McLellan, J.S. (登録日: 2025-01-07, 公開日: 2025-04-16)

主引用文献

Goldsmith, J.A.,Nguyen, A.W.,Wilen, R.E.,Wijagkanalan, W.,McLellan, J.S.,Maynard, J.A.
Structural basis for neutralizing antibody binding to pertussis toxin.
Proc.Natl.Acad.Sci.USA, 122:e2419457122-e2419457122, 2025

PubMed Abstract: Pertussis toxin (PT) is a key protective antigen in vaccine- and natural immunity-mediated protection from infection. Despite its importance, no PT-neutralizing epitopes have been characterized structurally. To define neutralizing epitopes and identify key structural elements to preserve during PT antigen design, we determined a 3.6 Å cryoelectron microscopy structure of genetically detoxified PT (PTg) bound to hu11E6 and hu1B7, two potently neutralizing anti-PT antibodies with complementary mechanisms: disruption of toxin adhesion to cells and intracellular activities, respectively. Hu11E6 binds the paralogous S2 and S3 subunits of PTg via a conserved epitope but surprisingly did not span the previously identified sialic acid-binding site implicated in toxin adhesion. Hu11E6 specifically prevented PTg binding to sialylated N-glycans and a sialylated model receptor, as demonstrated by high-throughput glycan array analysis and ELISA, while a T cell activation assay showed that it blocks PTg mitogenic activities to define its neutralizing mechanism. Hu1B7 bound a quaternary epitope spanning the S1 and S5 subunits, although functional studies of hu1B7 variants suggested that S5 binding is not involved in its PT neutralization mechanism. These results structurally define neutralizing epitopes on PT, improving our molecular understanding of immune protection from and providing key information for the future development of PT immunogens.

PubMed: 40172968
DOI: 10.1073/pnas.2419457122

実験手法

ELECTRON MICROSCOPY (3.56 Å)