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  CryoEM structures of membrane pore and prepore complex reveal cytolytic mechanism of Pneumolysin

van Pee, K., Neuhaus, A., D'Imprima, E., Mills, D. J., Kühlbrandt, W., & Yildiz, Ö. (2017). CryoEM structures of membrane pore and prepore complex reveal cytolytic mechanism of Pneumolysin. eLife, 6:. doi:10.7554/eLife.23644.001.

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資料種別: 学術論文

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 作成者:
van Pee, Katharina1, 著者           
Neuhaus, Alexander1, 著者           
D'Imprima, Edoardo1, 著者           
Mills, Deryck J.1, 著者                 
Kühlbrandt, Werner1, 著者                 
Yildiz, Özkan1, 著者                 
所属:
1Department of Structural Biology, Max Planck Institute of Biophysics, Max Planck Society, ou_2068291              

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キーワード: X-ray crystallography; biophysics; cholesterol-dependent cytolysin (CDC); electron cryo-microscopy (cryoEM); electron cryo-tomography (cryoET); infectious disease; membrane pore; microbiology; pore-forming toxin; structural biology
 要旨: Many pathogenic bacteria produce pore-forming toxins to attack and kill human cells. We have determined the 4.5 Å structure of the ~2.2 MDa pore complex of pneumolysin, the main virulence factor of Streptococcus pneumoniae, by cryoEM. The pneumolysin pore is a 400 Å ring of 42 membrane-inserted monomers. Domain 3 of the soluble toxin refolds into two ~85 Å β-hairpins that traverse the lipid bilayer and assemble into a 168-strand β-barrel. The pore complex is stabilized by salt bridges between β-hairpins of adjacent subunits and an internal α-barrel. The apolar outer barrel surface with large sidechains is immersed in the lipid bilayer, while the inner barrel surface is highly charged. Comparison of the cryoEM pore complex to the prepore structure obtained by electron cryo-tomography and the x-ray structure of the soluble form reveals the detailed mechanisms by which the toxin monomers insert into the lipid bilayer to perforate the target membrane.

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言語: eng - English
 日付: 20172016-11-282017-03-172017-03-21
 出版の状態: オンラインで出版済み
 ページ: 22
 出版情報: -
 目次: -
 査読: 査読あり
 識別子(DOI, ISBNなど): DOI: 10.7554/eLife.23644.001
 学位: -

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出版物名: eLife
種別: 学術雑誌
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出版社, 出版地: Cambridge : eLife Sciences Publications
ページ: - 巻号: 6 通巻号: e23644 開始・終了ページ: - 識別子(ISBN, ISSN, DOIなど): その他: 2050-084X
CoNE: https://pure.mpg.de/cone/journals/resource/2050-084X