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

Nat Commun. 2016 Jul 13:7:12062. doi: 10.1038/ncomms12062.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aeromonas hydrophila
  • Bacterial Toxins
  • Cryoelectron Microscopy*
  • Crystallography, X-Ray
  • Hydrophobic and Hydrophilic Interactions
  • Image Processing, Computer-Assisted
  • Models, Molecular
  • Pore Forming Cytotoxic Proteins / ultrastructure*
  • Protein Folding
  • Protein Structure, Tertiary*

Substances

  • Bacterial Toxins
  • Pore Forming Cytotoxic Proteins
  • aerolysin