Fig. 4.

Megalysins are pore-forming toxins. (A) Monomeric structures of four M. opercularis megalysins predicted by Alphafold 2. (B) Crystal structures of monomeric aerolysin-like proteins from bacteria and vertebrates (from left PDB 2ztb, 1uyj, 5zu4, 3c0o). (C) Monomeric structure of Mo12 predicted by Alphafold 2, rainbow display from the N terminus (blue) to C terminus (red). (D) Crystal structure of monomeric B. thuringiensis parasporin-2 (PDB 2ztb, left, rainbow display as in C with α-helices and β-strands marked. The three domains are indicated (Center), and a ribbon diagram is shown (Right). (E) Crystal structure of heptameric aerolysin (PDB 5jzt) showing alternating hydrophobic (yellow) and hydrophilic (green) residues that allow formation of a β-barrel pore. The alignment and hydropathy plot (Lower) demonstrate conservation of this sequence feature in megalysins. (F) Domain 1 aromatic patches of parasporin-2 (PDB 2ztb, Top Left) and Mo12 (Top Right). Alignment shows conservation of this sequence feature, which is thought to function in initial membrane binding, in megalysins.