EMD-0547
Helicobacter pylori Vacuolating Cytotoxin A Oligomeric Assembly 2e (OA-2e)
EMD-0547
Single-particle3.5 Å
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Map released: 27/03/2019
Last modified: 16/10/2024
Sample Organism:
Helicobacter pylori
Sample: Helicobacter pylori Vacuolating Cytotoxin A Oligomeric Assembly 2e (OA-2e)
Fitted models: 6nyn (Avg. Q-score: 0.376)
Raw data: EMPIAR-10607
Deposition Authors: Zhang K
,
Zhang H
Sample: Helicobacter pylori Vacuolating Cytotoxin A Oligomeric Assembly 2e (OA-2e)
Fitted models: 6nyn (Avg. Q-score: 0.376)
Raw data: EMPIAR-10607
Deposition Authors: Zhang K
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Cryo-EM structures ofHelicobacter pylorivacuolating cytotoxin A oligomeric assemblies at near-atomic resolution.
Zhang K
,
Zhang H,
Li S
,
Pintilie GD,
Mou TC,
Gao Y,
Zhang Q,
van den Bedem H
,
Schmid MF
,
Au SWN
,
Chiu W
(2019) PNAS , 116 , 6800 - 6805
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(2019) PNAS , 116 , 6800 - 6805
Abstract:
Human gastric pathogen Helicobacter pylori (H. pylori) 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 H. pylori 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.
Human gastric pathogen Helicobacter pylori (H. pylori) 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 H. pylori 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.