A unique fold of phospholipase C-beta mediates dimerization and interaction with G alpha q.

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.
Mesh Terms:
Amino Acid Sequence, Animals, Crystallography, X-Ray, Dimerization, GTP-Binding Protein alpha Subunits, Gq-G11, Heterotrimeric GTP-Binding Proteins, Isoenzymes, Models, Molecular, Molecular Sequence Data, Molecular Weight, Phospholipase C beta, Protein Binding, Protein Structure, Quaternary, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Alignment, Static Electricity, Turkeys, Type C Phospholipases
Nat. Struct. Biol.
Date: Jan. 01, 2002
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