4gnk
Crystal structure of Galphaq in complex with full-length human PLCbeta3Crystal structure of Galphaq in complex with full-length human PLCbeta3
Structural highlights
FunctionGNAQ_MOUSE Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro).[1] [2] Publication Abstract from PubMedPhospholipase C-beta (PLCbeta) is directly activated by Galphaq, but the molecular basis for how its distal C-terminal domain (CTD) contributes to maximal activity is poorly understood. Herein we present both the crystal structure and cryo-EM three-dimensional reconstructions of human full-length PLCbeta3 in complex with mouse Galphaq. The distal CTD forms an extended monomeric helical bundle consisting of three antiparallel segments with structural similarity to membrane-binding bin-amphiphysin-Rvs (BAR) domains. Sequence conservation of the distal CTD suggests putative membrane and protein interaction sites, the latter of which bind the N-terminal helix of Galphaq in both the crystal structure and cryo-EM reconstructions. Functional analysis suggests that the distal CTD has roles in membrane targeting and in optimizing the orientation of the catalytic core at the membrane for maximal rates of lipid hydrolysis. Full-length Galpha(q)-phospholipase C-beta3 structure reveals interfaces of the C-terminal coiled-coil domain.,Lyon AM, Dutta S, Boguth CA, Skiniotis G, Tesmer JJ Nat Struct Mol Biol. 2013 Mar;20(3):355-62. doi: 10.1038/nsmb.2497. Epub 2013 Feb, 3. PMID:23377541[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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