Activation of Escherichia coli prohaemolysin to the mature toxin by acyl carrier protein-dependent fatty acylation

Nature. 1991 Jun 27;351(6329):759-61. doi: 10.1038/351759a0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Carrier Protein / metabolism*
  • Acyl Carrier Protein / pharmacology
  • Acylation
  • Acyltransferases / metabolism
  • Amino Acid Sequence
  • Bacterial Proteins / metabolism*
  • Bacterial Toxins / metabolism
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins*
  • Fatty Acids / metabolism*
  • Hemolysin Proteins / metabolism*
  • Molecular Sequence Data
  • Myristic Acid
  • Myristic Acids / metabolism
  • Palmitic Acid
  • Palmitic Acids / metabolism
  • Protein Precursors / metabolism*
  • Protein Processing, Post-Translational

Substances

  • Acyl Carrier Protein
  • Bacterial Proteins
  • Bacterial Toxins
  • Escherichia coli Proteins
  • Fatty Acids
  • Hemolysin Proteins
  • Hlya protein, E coli
  • Myristic Acids
  • Palmitic Acids
  • Protein Precursors
  • Myristic Acid
  • Palmitic Acid
  • Acyltransferases