1jad

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1jad, resolution 2.40Å

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C-terminal Domain of Turkey PLC-beta

Overview

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.

About this Structure

1JAD is a Single protein structure of sequence from Meleagris gallopavo with as ligand. Active as Phosphoinositide phospholipase C, with EC number 3.1.4.11 Full crystallographic information is available from OCA.

Reference

A unique fold of phospholipase C-beta mediates dimerization and interaction with G alpha q., Singer AU, Waldo GL, Harden TK, Sondek J, Nat Struct Biol. 2002 Jan;9(1):32-6. PMID:11753430

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