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Structural basis for pore-forming mechanism of staphylococcal α-hemolysin

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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
Type: article (author version)
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)

Submitter: 田中 良和

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