E. coli hemolysin interactions with prokaryotic and eukaryotic cell membranes.
The hemolysin toxin (HlyA) is secreted across both the cytoplasmic and outer membranes of pathogenic Escherichia coli and forms membrane pores in cells of the host immune system, causing cell dysfunction and death. The processes underlying the interaction of HlyA with the bacterial and mammalian cell membranes are remarkable. Secretion of HlyA occurs without a periplasmic intermediate and is directed by an uncleaved C-terminal targetting signal and the HlyB and HlyD translocator proteins, the former being a member of a transporter superfamily central to import and export of a wide range of substrates by prokaryotic and eukaryotic cells. The separate process by which HlyA is targetted to mammalian cell membranes is dependent upon fatty acylation of a non-toxic precursor, proHlyA. This is achieved by a novel mechanism directed by the activator protein HlyC, which binds to an internal proHlyA recognition sequence and provides specificity for the transfer of fatty acid from cellular acyl carrier protein.
Hughes
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Cambridge University Department of Pathology, UK.
Stanley
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Koronakis
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D000215:Acylation; D000217:Acyltransferases; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000494:pharmacology* / Q000502:physiology; D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects*; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins; D005057:Eukaryotic Cells / Q000187:drug effects* / Q000648:ultrastructure; D015964:Gene Expression Regulation, Bacterial; D006460:Hemolysin Proteins / Q000494:pharmacology* / Q000502:physiology; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D011387:Prokaryotic Cells / Q000187:drug effects* / Q000648:ultrastructure; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000502:physiology
D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; C065231:HlyD protein, E coli; C036507:Hlya protein, E coli; C050837:Hlyb protein, Bacteria; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D011498:Protein Precursors; D021382:Protein Sorting Signals; D000217:Acyltransferases; C092237:HlyC protein, E coli