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-Structure paper
タイトル | Cryo-EM structures of vacuolating cytotoxin A oligomeric assemblies at near-atomic resolution. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 116, Issue 14, Page 6800-6805, Year 2019 |
掲載日 | 2019年4月2日 |
著者 | Kaiming Zhang / Huawei Zhang / Shanshan Li / Grigore D Pintilie / Tung-Chung Mou / Yuanzhu Gao / Qinfen Zhang / Henry van den Bedem / Michael F Schmid / Shannon Wing Ngor Au / Wah Chiu / |
PubMed 要旨 | 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 ...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. |
リンク | Proc Natl Acad Sci U S A / PubMed:30894496 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.2 - 9.9 Å |
構造データ | EMDB-0542, PDB-6nyf: EMDB-0543, PDB-6nyg: EMDB-0544, PDB-6nyj: EMDB-0545, PDB-6nyl: EMDB-0546, PDB-6nym: EMDB-0547, PDB-6nyn: EMDB-0548: EMDB-0549: EMDB-0550: EMDB-0551: |
由来 |
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キーワード | TOXIN / Helicobacter pylori / vacuolating cytotoxin A / pore-forming toxin |