title: Inositol hexakisphosphate (InsP6) can weaken the Ca(2+)-dependent membrane binding of C2AB domain of synaptotagmin I.
abstract: The synaptic vesicle protein synaptotagmin I has been proposed to serve as a Ca(2+) sensor for rapid exocytosis. In the present work, two fragments of the large cytoplasmic domain of synaptotagmin I, C2A and C2AB, were compared by combining surface plasmon resonance with circular dichroism and fluorescence techniques. C2AB and C2A had almost identical membrane binding constants, indicating that C2A is the predominate domain to bind to negatively charged phospholipids. After reacting with inositol hexakisphosphate (InsP6) a conformational change of C2AB was detected in the presence of liposome. The InsP6 binding notably weakened the Ca(2+)-dependent C2AB-membrane interaction, which suggests that InsP6 may act as a modulator of neurotransmitter release by altering the state of synaptotagmin-phospholipid interaction.
authors.affiliation: Department of Biological Sciences and Biotechnology, State Key Laboratory of Biomembrane, Tsinghua University, 100084, Beijing, PR China
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Lu
authors.forename: Yuhong
authors.initials: Y
authors.lastname: He
authors.forename: Sen-fang
authors.initials: SF
authors.lastname: Sui
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002462:Cell Membrane / Q000378:metabolism*; D002942:Circular Dichroism; D008051:Lipid Bilayers; D008081:Liposomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D010833:Phytic Acid / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020349:Surface Plasmon Resonance; D050863:Synaptotagmin I; D050857:Synaptotagmins
chemical_list: D002135:Calcium-Binding Proteins; D008051:Lipid Bilayers; D008081:Liposomes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010743:Phospholipids; D011994:Recombinant Proteins; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; D050857:Synaptotagmins; D010833:Phytic Acid; D002118:Calcium