6RO0

CRYSTAL STRUCTURE OF GENETICALLY DETOXIFIED PERTUSSIS TOXIN GDPT.

6RO0 の概要

• エントリーDOI: 10.2210/pdb6ro0/pdb
• 分子名称: Pertussis toxin subunit 1, Islet-activating protein S2, Islet-activating protein S3, ... (7 entities in total)
• 機能のキーワード: toxin
• 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: 255671.79

構造登録者

Bertrand, T. (登録日: 2019-05-10, 公開日: 2020-06-03, 最終更新日: 2024-10-16)

主引用文献

Ausar, S.F.,Zhu, S.,Duprez, J.,Cohen, M.,Bertrand, T.,Steier, V.,Wilson, D.J.,Li, S.,Sheung, A.,Brookes, R.H.,Pedyczak, A.,Rak, A.,Andrew James, D.
Genetically detoxified pertussis toxin displays near identical structure to its wild-type and exhibits robust immunogenicity.
Commun Biol, 3:427-427, 2020

PubMed Abstract: The mutant gdPT R9K/E129G is a genetically detoxified variant of the pertussis toxin (PTx) and represents an attractive candidate for the development of improved pertussis vaccines. The impact of the mutations on the overall protein structure and its immunogenicity has remained elusive. Here we present the crystal structure of gdPT and show that it is nearly identical to that of PTx. Hydrogen-deuterium exchange mass spectrometry revealed dynamic changes in the catalytic domain that directly impacted NAD binding which was confirmed by biolayer interferometry. Distal changes in dynamics were also detected in S2-S5 subunit interactions resulting in tighter packing of B-oligomer corresponding to increased thermal stability. Finally, antigen stimulation of human whole blood, analyzed by a previously unreported mass cytometry assay, indicated broader immunogenicity of gdPT compared to pertussis toxoid. These findings establish a direct link between the conserved structure of gdPT and its ability to generate a robust immune response.

PubMed: 32759959
DOI: 10.1038/s42003-020-01153-3

実験手法

X-RAY DIFFRACTION (2.13 Å)