7z3j

Structure of crystallisable rat Phospholipase C gamma 1 in complex with inositol 1,4,5-trisphosphate

spinqualitylabelsall models 7z3j, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7z3j is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: CA, GOL, I3P Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PLCG1_RAT Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration (By similarity). Publication Abstract from PubMed PLCgamma enzymes are autoinhibited in resting cells and form key components of intracellular signaling that are also linked to disease development. Insights into physiological and aberrant activation of PLCgamma require understanding of an active, membrane-bound form, which can hydrolyze inositol-lipid substrates. Here, we demonstrate that PLCgamma1 cannot bind membranes unless the autoinhibition is disrupted. Through extensive molecular dynamics simulations and experimental evidence, we characterize membrane binding by the catalytic core domains and reveal previously unknown sites of lipid interaction. The identified sites act in synergy, overlap with autoinhibitory interfaces, and are shown to be critical for the phospholipase activity in cells. This work provides direct evidence that PLCgamma1 is inhibited through obstruction of its membrane-binding surfaces by the regulatory region and that activation must shift PLCgamma1 to a conformation competent for membrane binding. Knowledge of the critical sites of membrane interaction extends the mechanistic framework for activation, dysregulation, and therapeutic intervention. Characterization of the membrane interactions of phospholipase Cgamma reveals key features of the active enzyme.,Le Huray KIP, Bunney TD, Pinotsis N, Kalli AC, Katan M Sci Adv. 2022 Jun 24;8(25):eabp9688. doi: 10.1126/sciadv.abp9688. Epub 2022 Jun , 24. PMID:35749497 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phospholipase C

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