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Crystal structure of a lipin/Pah phosphatidic acid phosphatase by Khayyo, Valerie I.; Hoffmann, Reece M.; Wang, Huan; Bell, Justin A.; Burke, John E.; Reue, Karen; Airola, Michael V. V. is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Crystal structure of a lipin/Pah phosphatidic acid phosphatase about?
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.
Who reads Crystal structure of a lipin/Pah phosphatidic acid phosphatase?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Khayyo, Valerie I.; Hoffmann, Reece M.; Wang, Huan; Bell, Justin A.; Burke, John E.; Reue, Karen; Airola, Michael V. V.
- Publisher
- Nature Publishing Group; Springer Science and Business Media LLC; [London]: Nature Publishing Group, 2010-; Society for Mining, Metallurgy and Exploration Inc.; Research Square (ISSN 2041-1723)
- Published
- 2020
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)