National Institutes of Health/National Institute Of Allergy and Infectious Diseases
AI039657
米国
National Institutes of Health/National Institute of General Medical Sciences
T32GM08230
米国
National Institutes of Health/National Cancer Institute
CA116087
米国
National Institutes of Health/National Cancer Institute
T32CA119925
米国
National Institutes of Health/National Institute of General Medical Sciences
R35GM118089
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases
F31AI112324
米国
Other government
5I01BX000627
米国
引用
ジャーナル: J Mol Biol / 年: 2019 タイトル: Cryo-EM Analysis Reveals Structural Basis of Helicobacter pylori VacA Toxin Oligomerization. 著者: Min Su / Amanda L Erwin / Anne M Campbell / Tasia M Pyburn / Lauren E Salay / Jessica L Hanks / D Borden Lacy / David L Akey / Timothy L Cover / Melanie D Ohi / 要旨: Helicobacter pylori colonizes the human stomach and contributes to the development of gastric cancer and peptic ulcer disease. H. pylori secretes a pore-forming toxin called vacuolating cytotoxin A ...Helicobacter pylori colonizes the human stomach and contributes to the development of gastric cancer and peptic ulcer disease. H. pylori secretes a pore-forming toxin called vacuolating cytotoxin A (VacA), which contains two domains (p33 and p55) and assembles into oligomeric structures. Using single-particle cryo-electron microscopy, we have determined low-resolution structures of a VacA dodecamer and heptamer, as well as a 3.8-Å structure of the VacA hexamer. These analyses show that VacA p88 consists predominantly of a right-handed beta-helix that extends from the p55 domain into the p33 domain. We map the regions of p33 and p55 involved in hexamer assembly, model how interactions between protomers support heptamer formation, and identify surfaces of VacA that likely contact membrane. This work provides structural insights into the process of VacA oligomerization and identifies regions of VacA protomers that are predicted to contact the host cell surface during channel formation.