6NYF

Helicobacter pylori Vacuolating Cytotoxin A Oligomeric Assembly 1 (OA-1)

6NYF の概要

• エントリーDOI: 10.2210/pdb6nyf/pdb
• EMDBエントリー: 0542 0543 0544 0545 0546 0547 0548 0549 0550 0551
• 分子名称: Vacuolating cytotoxin autotransporter (1 entity in total)
• 機能のキーワード: helicobacter pylori, vacuolating cytotoxin a, pore-forming toxin, toxin
• 由来する生物種: Helicobacter pylori (Campylobacter pylori)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 530779.27

構造登録者

Zhang, K.,Zhang, H.,Li, S.,Au, S.,Chiu, W. (登録日: 2019-02-11, 公開日: 2019-03-27, 最終更新日: 2024-10-30)

主引用文献

Zhang, K.,Zhang, H.,Li, S.,Pintilie, G.D.,Mou, T.C.,Gao, Y.,Zhang, Q.,van den Bedem, H.,Schmid, M.F.,Au, S.W.N.,Chiu, W.
Cryo-EM structures ofHelicobacter pylorivacuolating cytotoxin A oligomeric assemblies at near-atomic resolution.
Proc. Natl. Acad. Sci. U.S.A., 116:6800-6805, 2019

PubMed Abstract: Human gastric pathogen () is the primary risk factor for gastric cancer and is one of the most prevalent carcinogenic infectious agents. Vacuolating cytotoxin A (VacA) is a key virulence factor secreted by and induces multiple cellular responses. Although structural and functional studies of VacA have been extensively performed, the high-resolution structure of a full-length VacA protomer and the molecular basis of its oligomerization are still unknown. Here, we use cryoelectron microscopy to resolve 10 structures of VacA assemblies, including monolayer (hexamer and heptamer) and bilayer (dodecamer, tridecamer, and tetradecamer) oligomers. The models of the 88-kDa full-length VacA protomer derived from the near-atomic resolution maps are highly conserved among different oligomers and show a continuous right-handed β-helix made up of two domains with extensive domain-domain interactions. The specific interactions between adjacent protomers in the same layer stabilizing the oligomers are well resolved. For double-layer oligomers, we found short- and/or long-range hydrophobic interactions between protomers across the two layers. Our structures and other previous observations lead to a mechanistic model wherein VacA hexamer would correspond to the prepore-forming state, and the N-terminal region of VacA responsible for the membrane insertion would undergo a large conformational change to bring the hydrophobic transmembrane region to the center of the oligomer for the membrane channel formation.

PubMed: 30894496
DOI: 10.1073/pnas.1821959116

実験手法

ELECTRON MICROSCOPY (3.2 Å)