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http://purl.uniprot.org/citations/18945677http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18945677http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18945677http://www.w3.org/2000/01/rdf-schema#comment"Rabphilin-3A is a neuronal C2 domain tandem containing protein involved in vesicle trafficking. Both its C2 domains (C2A and C2B) are able to bind phosphatidylinositol 4,5-bisphosphate, a key player in the neurotransmitter release process. The rabphilin-3A C2A domain has previously been shown to bind inositol-1,4,5-trisphosphate (IP3; phosphatidylinositol 4,5-bisphosphate headgroup) in a Ca2+-dependent manner with a relatively high affinity (50 microm) in the presence of saturating concentrations of Ca2+. Moreover, IP3 and Ca2+ binding to the C2A domain mutually enhance each other. Here we present the Ca2+-bound solution structure of the C2A domain. Structural comparison with the previously published Ca2+-free crystal structure revealed that Ca2+ binding induces a conformational change of Ca2+ binding loop 3 (CBL3). Our IP3 binding studies as well as our IP3-C2A docking model show the active involvement of CBL3 in IP3 binding, suggesting that the conformational change on CBL3 upon Ca2+ binding enables the interaction with IP3 and vice versa, in line with a target-activated messenger affinity mechanism. Our data provide detailed structural insight into the functional properties of the rabphilin-3A C2A domain and reveal for the first time the structural determinants of a target-activated messenger affinity mechanism."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m804094200"xsd:string
http://purl.uniprot.org/citations/18945677http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m804094200"xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/author"Becker S."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/author"Becker S."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/author"Zweckstetter M."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/author"Zweckstetter M."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/author"Coudevylle N."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/author"Coudevylle N."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/author"Montaville P."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/author"Montaville P."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/author"Leonov A."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/author"Leonov A."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/pages"35918-35928"xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/pages"35918-35928"xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/title"Structural determinants for Ca2+ and phosphatidylinositol 4,5-bisphosphate binding by the C2A domain of rabphilin-3A."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/title"Structural determinants for Ca2+ and phosphatidylinositol 4,5-bisphosphate binding by the C2A domain of rabphilin-3A."xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/volume"283"xsd:string
http://purl.uniprot.org/citations/18945677http://purl.uniprot.org/core/volume"283"xsd:string