7Z3J
Structure of crystallisable rat Phospholipase C gamma 1 in complex with inositol 1,4,5-trisphosphate
Summary for 7Z3J
| Entry DOI | 10.2210/pdb7z3j/pdb |
| Descriptor | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1, CALCIUM ION, D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | hydrolase complex autoinhibited state, hydrolase |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 1 |
| Total formula weight | 136767.47 |
| Authors | Pinotsis, N.,Bunney, T.D.,Katan, M. (deposition date: 2022-03-02, release date: 2022-07-20, Last modification date: 2024-10-23) |
| Primary citation | Le Huray, K.I.P.,Bunney, T.D.,Pinotsis, N.,Kalli, A.C.,Katan, M. Characterization of the membrane interactions of phospholipase C gamma reveals key features of the active enzyme. Sci Adv, 8:eabp9688-eabp9688, 2022 Cited by PubMed Abstract: PLCγ 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 PLCγ require understanding of an active, membrane-bound form, which can hydrolyze inositol-lipid substrates. Here, we demonstrate that PLCγ1 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 PLCγ1 is inhibited through obstruction of its membrane-binding surfaces by the regulatory region and that activation must shift PLCγ1 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. PubMed: 35749497DOI: 10.1126/sciadv.abp9688 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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