6NYJ

Helicobacter pylori Vacuolating Cytotoxin A Oligomeric Assembly 2b (OA-2b)

Summary for 6NYJ

• Entry DOI: 10.2210/pdb6nyj/pdb
• EMDB information: 0542 0543 0544 0545 0546 0547 0548 0549 0550 0551
• Descriptor: Vacuolating cytotoxin autotransporter (1 entity in total)
• Functional Keywords: helicobacter pylori, vacuolating cytotoxin a, pore-forming toxin, toxin
• Biological source: Helicobacter pylori (Campylobacter pylori)
• Total number of polymer chains: 12
• Total formula weight: 1061558.53

Authors

Zhang, K.,Zhang, H.,Li, S.,Au, S.,Chiu, W. (deposition date: 2019-02-11, release date: 2019-03-27, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.2 Å)