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| Nat. Struct. Biol. Jan (2002); 9(1):32-6 | |
| A unique fold of phospholipase C-beta mediates dimerization and interaction with G alpha q. | |
| Singer AU, Waldo GL, Harden TK, Sondek J | |
| Department of Pharmacology, The University of North Carolina at Chapel Hill, North Carolina 27599, USA. | |
| Abstract: GTP-bound subunits of the Gq family of G alpha subunits directly activate phospholipase C-beta (PLC-beta) isozymes to produce the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. PLC-betas are GTPase activating proteins (GAPs) that also promote the formation of GDP-bound, inactive G beta subunits. Both phospholipase activation by G alpha-GTP subunits and GAP activity require a C-terminal region unique to PLC-beta isozymes. The crystal structure of the C-terminal region from an avian PLC-beta, determined at 2.4 A resolution, reveals a novel fold composed almost entirely of three long helices forming a coiled-coil that dimerizes along its long axis in an antiparallel orientation. The dimer interface is extensive ( approximately 3,200 A(2)), and, based on gel exclusion chromatography, full length PLC-betas are dimeric, indicating that PLC-betas likely function as dimers. Sequence conservation, mutational data and molecular modeling show that an electrostatically positive surface of the dimer contains the major determinants for binding G beta q. Effector dimerization, as highlighted by PLC-betas, provides a viable mechanism for regulating signaling cascades linked to heterotrimeric G proteins. | |
| [PUBMED: 11753430] |   |
| Copyright © 2009, Tyers Lab, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, All Rights Reserved. |
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| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |