Extending the Aerolysin Family: From Bacteria to Vertebrates

Abstract

A number of bacterial virulence factors have been observed to adopt structures similar to that of aerolysin, the principal toxin of Aeromonas species. However, a comprehensive description of architecture and structure of the aerolysin-like superfamily has not been determined. In this study, we define a more compact aerolysin-like domain – or aerolysin fold – and show that this domain is far more widely spread than anticipated since it can be found throughout kingdoms. The aerolysin-fold could be found in very diverse domain and functional contexts, although a toxic function could often be assigned. Due to this diversity, the borders of the superfamily could not be set on a sequence level. As a border-defining member, we therefore chose pXO2-60 – a protein from the pathogenic pXO2 plasmid of Bacillus anthracis. This fascinating protein, which harbors a unique ubiquitin-like fold domain at the C-terminus of the aerolysin-domain, nicely illustrates the diversity of the superfamily. Its putative role in the virulence of B. anthracis and its three dimensional model are discussed.

Host-derived, pore-forming toxin–like protein and trefoil factor complex protects the host against microbial infection

“…1B). Indeed, the aerolysin domain-containing proteins are widely distributed, from bacteria to vertebrates (9) (Table S1). Specifically, the aerolysin domain of βγ-CAT showed high similarity to the aerolysin domains of other vertebrate proteins (Fig.…”

“…NLR-dependent (NLRP3-dependent in mammals) caspase-1 activation and IL-1β release have been associated with destabilization of the lysosomal membrane and activation of lysosomal proteases (specifically, cathepsin B) (6). The βγ-CAT α-subunit consists of structural elements that tend to undergo oligomerization and insert into the membrane to form pores (9,30,31). Previous studies have shown that, whereas the β-subunit of βγ-CAT is most likely responsible for binding to cells via "protein" receptor(s), its α-subunit formed transmembrane pores in anucleate erythrocyte and platelet membranes, which resulted in rapid K + efflux (10,11,32).…”

“…Interestingly, various proteins containing aerolysin domains that undergo fusion with other domains have been discovered in vertebrates (9) (Table S1 and Fig. S1A).…”

“…The aerolysin domain is defined according to its structural similarity to the transmembrane domain of aerolysin toxins. Strikingly, a diverse array of proteins harboring an aerolysin domain fused with other domains have been identified in various vertebrate species (9). Similar to the α-subunit of βγ-CAT, ep37 proteins from the amphibian newt Cynops pyrrhogaster harbor an aerolysin domain fused to two N-terminal βγ-crystallin domains that share structural similarity with eye lens βγ-crystallins (14).…”

Structural classification of insecticidal proteins – Towards an in silico characterisation of novel toxins

“…In the aerolysin family of proteins, the conserved beta sheet dominated aerolysin fold is believed to adopt a barrel conformation within a membrane with the associated domains primarily having a binding role (Szczesny et al, 2011). It is conceivable that despite the diversity in primary sequence, many of the non 3-domain Cry toxins could share significant structural/functional homology.…”