1.C.59.3.1
The β-barrel pore-forming toxin (PFP), Monalysin.  The soluble monomer is cleaved to yield oligomeric pores.  The structure of a cleaved form lacking the transmembrane domain has been solved by x-ray crystalography and cryo-EM (PDB#4MJT; Leone et al. 2015).  The structure displays an elongated shape, resembling those of beta-pore-forming toxins such as aerolysin, but it lacks the receptor binding domain. Pro-monalysin forms a stable doughnut-like 18-mer complex composed of two disk-shaped nonamers held together by N-terminal swapping of the pro-peptides. This is in contrast with the monomeric pro-form of the other beta-PFTs that are receptor-dependent for membrane interaction. The membrane-spanning region of pro-monalysin is fully buried in the center of the doughnut, suggesting that upon pro-peptide cleavage, the two disk-shaped nonamers can - and have to - dissociate to leave the transmembrane segments free to deploy and lead to pore formation. In contrast with other toxins, the delivery of 18 subunits at once, nearby the cell surface, may be used to by-pass the requirement for a receptor-dependent concentration to reach the threshold for oligomerization into the pore-forming complex (Leone et al. 2015).