6tzy

Crystal Structure of a lipin/Pah Phosphatidic Acid Phosphatase

spinqualitylabelsall models 6tzy, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6tzy is a 4 chain structure with sequence from Tetrahymena thermophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3Å Ligands: CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function I7MFJ3_TETTS Publication Abstract from PubMed Lipin/Pah phosphatidic acid phosphatases (PAPs) generate diacylglycerol to regulate triglyceride synthesis and cellular signaling. Inactivating mutations cause rhabdomyolysis, autoinflammatory disease, and aberrant fat storage. Disease-mutations cluster within the conserved N-Lip and C-Lip regions that are separated by 500-residues in humans. To understand how the N-Lip and C-Lip combine for PAP function, we determined crystal structures of Tetrahymena thermophila Pah2 (Tt Pah2) that directly fuses the N-Lip and C-Lip. Tt Pah2 adopts a two-domain architecture where the N-Lip combines with part of the C-Lip to form an immunoglobulin-like domain and the remaining C-Lip forms a HAD-like catalytic domain. An N-Lip C-Lip fusion of mouse lipin-2 is catalytically active, which suggests mammalian lipins function with the same domain architecture as Tt Pah2. HDX-MS identifies an N-terminal amphipathic helix essential for membrane association. Disease-mutations disrupt catalysis or destabilize the protein fold. This illustrates mechanisms for lipin/Pah PAP function, membrane association, and lipin-related pathologies. Crystal structure of a lipin/Pah phosphatidic acid phosphatase.,Khayyo VI, Hoffmann RM, Wang H, Bell JA, Burke JE, Reue K, Airola MV Nat Commun. 2020 Mar 11;11(1):1309. doi: 10.1038/s41467-020-15124-z. PMID:32161260 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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