Identification of a membrane-bound prepore species clarifies the lytic mechanism of actinoporins

Koldo Morante, Augusto Bellomio, David Gil-Cartón, Lorena Redondo-Morata, Jesús Sot, Simon Scheuring, Mikel Valle, Juan Manuel González-Mañas, Kouhei Tsumoto, Jose M.M. Caaveiro

研究成果: ジャーナルへの寄稿記事

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Pore-forming toxins (PFTs) are cytolytic proteins belonging to the molecular warfare apparatus of living organisms. The assembly of the functional transmembrane pore requires several intermediate steps ranging from a water-soluble monomeric species to the multimeric ensemble inserted in the cell membrane. The non-lytic oligomeric intermediate known as prepore plays an essential role in the mechanism of insertion of the class of β-PFTs. However, in the class of α-PFTs, like the actinoporins produced by sea anemones, evidence of membrane-bound prepores is still lacking. We have employed single-particle cryo-electron microscopy (cryo-EM) and atomic force microscopy to identify, for the first time, a prepore species of the actinoporin fragaceatoxin C bound to lipid vesicles. The size of the prepore coincides with that of the functional pore, except for the transmembrane region, which is absent in the prepore. Biochemical assays indicated that, in the prepore species, the N terminus is not inserted in the bilayer but is exposed to the aqueous solution. Our study reveals the structure of the prepore in actinoporins and highlights the role of structural intermediates for the formation of cytolytic pores by an α-PFT.

元の言語英語
ページ(範囲)19210-19219
ページ数10
ジャーナルJournal of Biological Chemistry
291
発行部数37
DOI
出版物ステータス出版済み - 9 9 2016

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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