title: Activation of Escherichia coli prohaemolysin to the mature toxin by acyl carrier protein-dependent fatty acylation.
abstract: Haemolysin secreted by pathogenic Escherichia coli binds to mammalian cell membranes, disrupting cellular activities and lysing cells by pore-formation. It is synthesized as nontoxic prohaemolysin (proHlyA), which is activated intracellularly by a mechanism dependent on the cosynthesized HlyC. Haemolysin is one of a family of membrane-targeted toxins, including the leukotoxins of Pasteurella and Actinobacillus and the bifunctional adenylate cyclase haemolysin of Bordetella pertussis, which require this protoxin activation 1-5. HlyC alone cannot activate proHlyA, but requires a cytosolic activating factor6. Here we report the cytosolic activating factor is identical to the acyl carrier protein and that activation to mature toxin is achieved by the transfer of a fatty acyl group from acyl carrier protein to proHlyA. Only acyl carrier protein, not acyl-CoA, can promote HlyC-directed proHlyA acylation, but a range of acyl groups are effective.
authors.affiliation: Department of Pathology, University of Cambridge, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Issartel
authors.forename: V
authors.initials: V
authors.lastname: Koronakis
authors.forename: C
authors.initials: C
authors.lastname: Hughes
mesh_terms: D000213:Acyl Carrier Protein / Q000378:metabolism* / Q000494:pharmacology; D000215:Acylation; D000217:Acyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D005227:Fatty Acids / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D000213:Acyl Carrier Protein; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D005227:Fatty Acids; D006460:Hemolysin Proteins; C036507:Hlya protein, E coli; D009227:Myristic Acids; D010169:Palmitic Acids; D011498:Protein Precursors; D019814:Myristic Acid; D019308:Palmitic Acid; D000217:Acyltransferases