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

Preview

Text ncomms12062.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (1MB) | Preview

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.

Interest & Impact

Downloads

255 since deposited on 02 Aug 2016
12 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item