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Structural basis for pore-forming mechanism of staphylococcal α-hemolysin
This item is licensed under:Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
| Title: | Structural basis for pore-forming mechanism of staphylococcal α-hemolysin |
| Authors: | Sugawara, Takaki Browse this author | | Yamashita, Daichi Browse this author | | Kato, Koji Browse this author | | Peng, Zhao Browse this author | | Ueda, Junki Browse this author | | Kaneko, Jun Browse this author | | Kamio, Yoshiyuki Browse this author | | Tanaka, Yoshikazu Browse this author →KAKEN DB | | Yao, Min Browse this author |
| Keywords: | Staphylococcal α-hemolysin | | Pore-forming toxin | | Crystal structure |
| Issue Date: | 15-Dec-2015 |
| Publisher: | Elsevier |
| Journal Title: | Toxicon |
| Volume: | 108 |
| Start Page: | 226 |
| End Page: | 231 |
| Publisher DOI: | 10.1016/j.toxicon.2015.09.033 |
| PMID: | 26428390 |
| Abstract: | Staphylococcal alpha-hemolysin (alpha-HL) is a beta-barrel pore-forming toxin (PFT) expressed by Staphylococcus aureus. alpha-HL is secreted as a water-soluble monomeric protein, which binds to target membranes and forms membrane-inserted heptameric pores. To explore the pore-forming mechanism of alpha-HL in detail, we determined the crystal structure of the alpha-HL monomer and prepore using H35A mutant and W179A/R200A mutant, respectively. Although the overall structure of the monomer was similar to that of other staphylococcal PFTs, a marked difference was observed in the N-terminal amino latch, which bent toward the prestem. Moreover, the prestem was fastened by the cap domain with a key hydrogen bond between Asp45 and Tyr118. Prepore structure showed that the transmembrane region is roughly formed with flexibility, although the upper half of the beta-barrel is formed appropriately. Structure comparison among monomer, prepore and pore revealed a series of motions, in which the N-terminal amino latch released upon oligomerization destroys its own key hydrogen bond between Asp45 Tyr118. This action initiated the protrusion of the prestem. Y118F mutant and the N-terminal truncated mutant markedly decreased in the hemolytic activity, indicating the importance of the key hydrogen bond and the N-terminal amino latch on the pore formation. Based on these observations, we proposed a dynamic molecular mechanism of pore formation for alpha-HL. |
| Rights: | © 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/63926 |
| Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 田中 良和
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