Aerolysin nanopore structure revealed at high resolution in lipid environment

Abstract

AbstractAerolysin is a β-pore-forming toxin produced by mostAeromonasbacteria which has attracted large attention in the field of nanopore sensing due to its narrow and charged pore lumen. Structurally similar proteins, belonging to the aerolysin-like family, are present throughout all kingdoms of life, but very few of them have been structurally characterized in a lipid environment. Here we present the first high-resolution atomic cryo-EM structures of aerolysin pre-pore and pore in a membrane-like environment. These structures allow the identification of key interactions, which are relevant for the pore formation and for positioning the pore barrel into the membrane with the anchoring β-turn motif now finally observed. Moreover, we elucidate at high resolution the architecture of key mutations and precisely identify four constriction rings in the pore lumen that are highly relevant for nanopore sensing experiments.