Molecular basis of transmembrane beta-barrel formation of staphylococcal pore-forming toxins

• Yamashita, Daichi

• Sugawara, Takaki

• Takeshita, Miyu

• Kaneko, Jun

• Kamio, Yoshiyuki

• Tanaka, Isao

• Tanaka, Yoshikazu

• Yao, Min

抄録

Pathogenic bacteria secrete pore-forming toxins (PFTs) to attack target cells. PFTs are expressed as water-soluble monomeric proteins, which oligomerize into nonlytic prepore intermediates on the target cell membrane before forming membrane-spanning pores. Despite a wealth of biochemical data, the lack of high-resolution prepore structural information has hampered understanding of the beta-barrel formation process. Here, we report crystal structures of staphylococcal gamma-haemolysin and leucocidin prepores. The structures reveal a disordered bottom half of the beta-barrel corresponding to the transmembrane region, and a rigid upper extramembrane half. Spectroscopic analysis of fluorescently labelled mutants confirmed that the prepore is distinct from the pore within the transmembrane region. Mutational analysis also indicates a pivotal role for the glycine residue located at the lipid-solvent interface as a 'joint' between the two halves of the beta-barrel. These observations suggest a two-step transmembrane beta-barrel pore formation mechanism in which the upper extramembrane and bottom transmembrane regions are formed independently.

収録刊行物

• Nature Communications

  Nature Communications 5 4897-, 2014-09

  Nature Publishing Group

キーワード

• General Physics and Astronomy
• General Biochemistry, Genetics and Molecular Biology
• General Chemistry
• Multidisciplinary

詳細情報

• CRID: 1050564288970411776
• NII論文ID: 120005572422
• DOI: 10.1038/ncomms5897
• HANDLE: 2115/58223
• ISSN: 20411723
• Web Site: https://www.nature.com/articles/ncomms5897.pdf
• Web Site: https://www.nature.com/articles/ncomms5897
• 本文言語コード: en
• 資料種別: journal article
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