Cryo-EM structure of aerolysin variants reveals a novel protein fold and the pore-formation process

Iacovache, Mircea Ioan; De Carlo, Sacha; Cirauqui, Nuria; Dal Peraro, Matteo; van der Goot, F Gisou; Zuber, Benoît (2016). Cryo-EM structure of aerolysin variants reveals a novel protein fold and the pore-formation process. Nature communications, 7, p. 12062. Nature Publishing Group 10.1038/ncomms12062

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Owing to their pathogenical role and unique ability to exist both as soluble proteins and transmembrane complexes, pore-forming toxins (PFTs) have been a focus of microbiologists and structural biologists for decades. PFTs are generally secreted as water-soluble monomers and subsequently bind the membrane of target cells. Then, they assemble into circular oligomers, which undergo conformational changes that allow membrane insertion leading to pore formation and potentially cell death. Aerolysin, produced by the human pathogen Aeromonas hydrophila, is the founding member of a major PFT family found throughout all kingdoms of life. We report cryo-electron microscopy structures of three conformational intermediates and of the final aerolysin pore, jointly providing insight into the conformational changes that allow pore formation. Moreover, the structures reveal a protein fold consisting of two concentric β-barrels, tightly kept together by hydrophobic interactions. This fold suggests a basis for the prion-like ultrastability of aerolysin pore and its stoichiometry.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)

UniBE Contributor:

Iacovache, Mircea Ioan and Zuber, Benoît

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Benoît Zuber

Date Deposited:

02 Aug 2016 11:10

Last Modified:

14 Feb 2019 18:06

Publisher DOI:

10.1038/ncomms12062

PubMed ID:

27405240

BORIS DOI:

10.7892/boris.84558

URI:

https://boris.unibe.ch/id/eprint/84558

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