Inositol 1,4,5-trisphosphate directly opens diphtheria toxin channels.
Inositol 1,4,5-trisphosphate (IP3) is a soluble second messenger, which acts by cooperatively releasing Ca2+ into the cytosol from non-mitochondrial stores, probably by activating Ca(2+)-permeable channels. We demonstrate that submicromolar concentrations of IP3 can directly open the Ca(2+)-permeable diphtheria toxin channel, and that this occurs by IP3 binding to a specific site on the toxin protein. This provides a model for IP3-induced Ca2+ release and suggests that IP3-induced channel opening may play a role in diphtheria intoxication and in protein translocation across membranes.
Department of Psychiatry and Biobehavioral Sciences, UCLA Neuropsychiatric Institute, Los Angeles, CA.
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Kagan
D001665:Binding Sites / Q000187:drug effects; D004167:Diphtheria Toxin / Q000494:pharmacology* / Q000633:toxicity; D004553:Electric Conductivity; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D010710:Phosphates / Q000737:chemistry
D004167:Diphtheria Toxin; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D010710:Phosphates; D015544:Inositol 1,4,5-Trisphosphate