BIOMAT Database Logo BIOMAT Database Logo

Crystal structure of a lipin/Pah phosphatidic acid phosphatase. 2020

Valerie I Khayyo, and Reece M Hoffmann, and Huan Wang, and Justin A Bell, and John E Burke, and Karen Reue, and Michael V Airola
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA.

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.

UI MeSH Term Description Entries
D010711 Phosphatidate Phosphatase A phosphomonoesterase involved in the synthesis of triacylglycerols. It catalyzes the hydrolysis of phosphatidates with the formation of diacylglycerols and orthophosphate. EC 3.1.3.4. Phosphatidate Phosphohydrolase,Phosphatidic Acid Phosphatase,Phosphatidic Acid Phosphohydrolase,Phosphatase, Phosphatidate,Phosphatase, Phosphatidic Acid,Phosphohydrolase, Phosphatidate,Phosphohydrolase, Phosphatidic Acid
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072756 Protein Conformation, alpha-Helical A secondary structure of proteins that is a right-handed helix or coil, where each amino (N-H) group of the peptide backbone contributes a hydrogen bond to the carbonyl(C alpha-Helical Conformation, Protein,alpha-Helical Protein Conformation,alpha-Helical Structures,alpha-Helices,alpha-Helix,Conformation, Protein alpha-Helical,Conformation, alpha-Helical Protein,Conformations, Protein alpha-Helical,Conformations, alpha-Helical Protein,Protein Conformation, alpha Helical,Protein Conformations, alpha-Helical,alpha Helical Conformation, Protein,alpha Helical Protein Conformation,alpha Helical Structures,alpha Helices,alpha Helix,alpha-Helical Conformations, Protein,alpha-Helical Protein Conformations,alpha-Helical Structure
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D015800 Protozoan Proteins Proteins found in any species of protozoan. Proteins, Protozoan
D016808 Tetrahymena thermophila A species of ciliate protozoa used in genetic and cytological research. Tetrahymena thermophilas,thermophilas, Tetrahymena
D057809 HEK293 Cells A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5. 293T Cells,HEK 293 Cell Line,HEK 293 Cells,Human Embryonic Kidney Cell Line 293,Human Kidney Cell Line 293,293 Cell, HEK,293 Cells, HEK,293T Cell,Cell, 293T,Cell, HEK 293,Cell, HEK293,Cells, 293T,Cells, HEK 293,Cells, HEK293,HEK 293 Cell,HEK293 Cell
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies
D020134 Catalytic Domain The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. Active Site,Catalytic Core,Catalytic Region,Catalytic Site,Catalytic Subunit,Reactive Site,Active Sites,Catalytic Cores,Catalytic Domains,Catalytic Regions,Catalytic Sites,Catalytic Subunits,Core, Catalytic,Cores, Catalytic,Domain, Catalytic,Domains, Catalytic,Reactive Sites,Region, Catalytic,Regions, Catalytic,Site, Active,Site, Catalytic,Site, Reactive,Sites, Active,Sites, Catalytic,Sites, Reactive,Subunit, Catalytic,Subunits, Catalytic

Related Publications

Valerie I Khayyo, and Reece M Hoffmann, and Huan Wang, and Justin A Bell, and John E Burke, and Karen Reue, and Michael V Airola
The phosphatidic acid phosphatase lipin-1 facilitates inflammation-driven colon carcinogenesis.
September 2018, JCI insight,
Valerie I Khayyo, and Reece M Hoffmann, and Huan Wang, and Justin A Bell, and John E Burke, and Karen Reue, and Michael V Airola
Purification of Lipin and Measurement of Phosphatidic Acid Phosphatase Activity from Liposomes.
January 2018, Methods in enzymology,
Valerie I Khayyo, and Reece M Hoffmann, and Huan Wang, and Justin A Bell, and John E Burke, and Karen Reue, and Michael V Airola
Insulin controls subcellular localization and multisite phosphorylation of the phosphatidic acid phosphatase, lipin 1.
January 2007, The Journal of biological chemistry,
Valerie I Khayyo, and Reece M Hoffmann, and Huan Wang, and Justin A Bell, and John E Burke, and Karen Reue, and Michael V Airola
Phosphorylation of lipin 1 and charge on the phosphatidic acid head group control its phosphatidic acid phosphatase activity and membrane association.
April 2013, The Journal of biological chemistry,
Valerie I Khayyo, and Reece M Hoffmann, and Huan Wang, and Justin A Bell, and John E Burke, and Karen Reue, and Michael V Airola
[Phosphatidic acid phosphatase].
June 1999, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme,
Valerie I Khayyo, and Reece M Hoffmann, and Huan Wang, and Justin A Bell, and John E Burke, and Karen Reue, and Michael V Airola
Crystal structure of a mammalian purple acid phosphatase.
July 1999, Journal of molecular biology,
Valerie I Khayyo, and Reece M Hoffmann, and Huan Wang, and Justin A Bell, and John E Burke, and Karen Reue, and Michael V Airola
Liver-specific loss of lipin-1-mediated phosphatidic acid phosphatase activity does not mitigate intrahepatic TG accumulation in mice.
April 2015, Journal of lipid research,
Valerie I Khayyo, and Reece M Hoffmann, and Huan Wang, and Justin A Bell, and John E Burke, and Karen Reue, and Michael V Airola
Crystal structure of mammalian purple acid phosphatase.
July 1999, Structure (London, England : 1993),
Valerie I Khayyo, and Reece M Hoffmann, and Huan Wang, and Justin A Bell, and John E Burke, and Karen Reue, and Michael V Airola
Crystal structure of human prostatic acid phosphatase .
February 2000, The Prostate,
Valerie I Khayyo, and Reece M Hoffmann, and Huan Wang, and Justin A Bell, and John E Burke, and Karen Reue, and Michael V Airola
Pulmonary phosphatidic acid phosphatase. Properties of membrane-bound phosphatidate-dependent phosphatidic acid phosphatase in rat lung.
August 1979, Biochimica et biophysica acta,
Copied contents to your clipboard!