4MKQ: Crystal Structure Of The Pore-forming Toxin Monalysin Mutant Deleted Of The Membrane-spanning Domain

beta-Barrel pore-forming toxins (beta-PFT), a large family of bacterial toxins, are generally secreted as water-soluble monomers and can form oligomeric pores in membranes following proteolytic cleavage and interaction with cell surface receptors. Monalysin has been recently identified as a beta-PFT that contributes to the virulence of Pseudomonas entomophila against Drosophila. It is secreted as a pro-protein that becomes active upon cleavage. Here we report the crystal and cryo-electron microscopy structure of the pro-form of Monalysin as well as the crystal structures of the cleaved form and of an inactive mutant lacking the membrane-spanning region. The overall structure of Monalysin displays an elongated shape, which resembles those of beta-pore-forming toxins, such as Aerolysin, but is devoid of a receptor-binding domain. X-ray crystallography, cryo-electron microscopy, and light-scattering studies show that 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 observation 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 cleavage of pro-peptides, 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 bypass the requirement of receptor-dependent concentration to reach the threshold for oligomerization into the pore-forming complex.
PDB ID: 4MKQDownload
MMDB ID: 127600
PDB Deposition Date: 2013/9/5
Updated in MMDB: 2017/08
Experimental Method:
x-ray diffraction
Resolution: 2.65  Å
Source Organism:
Similar Structures:
Biological Unit for 4MKQ: octameric; determined by author and by software (PISA)
Molecular Components in 4MKQ
Label Count Molecule
Proteins (8 molecules)
Monalysin(Gene symbol: PSEEN_RS14675)
Molecule annotation
Monalysin(Gene symbol: PSEEN_RS14675)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB