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Publication Abstract from PubMed

Pathogenic bacteria secrete pore-forming toxins (PFTs) to attack target cells. PFTs are expressed as water-soluble monomeric proteins, which oligomerize into nonlytic prepore intermediates on the target cell membrane before forming membrane-spanning pores. Despite a wealth of biochemical data, the lack of high-resolution prepore structural information has hampered understanding of the beta-barrel formation process. Here, we report crystal structures of staphylococcal gamma-haemolysin and leucocidin prepores. The structures reveal a disordered bottom half of the beta-barrel corresponding to the transmembrane region, and a rigid upper extramembrane half. Spectroscopic analysis of fluorescently labelled mutants confirmed that the prepore is distinct from the pore within the transmembrane region. Mutational analysis also indicates a pivotal role for the glycine residue located at the lipid-solvent interface as a 'joint' between the two halves of the beta-barrel. These observations suggest a two-step transmembrane beta-barrel pore formation mechanism in which the upper extramembrane and bottom transmembrane regions are formed independently.

Molecular basis of transmembrane beta-barrel formation of staphylococcal pore-forming toxins.,Yamashita D, Sugawara T, Takeshita M, Kaneko J, Kamio Y, Tanaka I, Tanaka Y, Yao M Nat Commun. 2014 Sep 29;5:4897. doi: 10.1038/ncomms5897. PMID:25263813^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.