title: Protein disulphide isomerase binds ammodytoxin strongly: possible implications for toxin trafficking.
abstract: Ammodytoxin, a group IIA secreted phospholipase A(2) from the venom of the long-nosed viper (Vipera ammodytes ammodytes), is a potent presynaptically acting neurotoxin. It blocks the secretion of neurotransmitter from the nerve cell, thus hindering the communication with the neighbouring neuron or muscle cell. To express the neurotoxicity, ammodytoxin should interact with specific receptors in the axon terminal and express phospholipase activity. Our previous results indicate that, following the association with a receptor on the external side of the presynaptic membrane, the toxin penetrates into the cytosol of the nerve cell. Here, we show that the toxin associates specifically with protein disulphide isomerase, a protein in the lumen of endoplasmic reticulum, which may be crucial for the retention and concentration of the toxin in this cellular compartment and for its subsequent transport across the membrane of endoplasmic reticulum into the cytosol of the nerve cell.
authors.affiliation: Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Ljubljana, Slovenia.
authors.forename: Jernej
authors.initials: J
authors.lastname: Sribar
authors.forename: Gregor
authors.initials: G
authors.lastname: Anderluh
authors.forename: Jay W
authors.initials: JW
authors.lastname: Fox
authors.forename: Igor
authors.initials: I
authors.lastname: Krizaj
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism*; D004789:Enzyme Activation; D054501:Group II Phospholipases A2; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000737:chemistry*; D013552:Swine; D014757:Viper Venoms / Q000737:chemistry*
chemical_list: D014757:Viper Venoms; D054501:Group II Phospholipases A2; C060161:ammodytoxin C; D019704:Protein Disulfide-Isomerases