7kiq
Crystal structure of the mouse lipin-2 M-Lip domain
Structural highlights
FunctionLPIN2_MOUSE Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis in the reticulum endoplasmic membrane (PubMed:17158099). Plays important roles in controlling the metabolism of fatty acids at different levels. Acts also as a nuclear transcriptional coactivator for PPARGC1A to modulate lipid metabolism.[1] [2] [3] Publication Abstract from PubMedPhospholipid synthesis and fat storage as triglycerides are regulated by lipin phosphatidic acid phosphatases (PAPs), whose enzymatic PAP function requires association with cellular membranes. Using hydrogen deuterium exchange mass spectrometry, we find mouse lipin 1 binds membranes through an N-terminal amphipathic helix, the Ig-like domain and HAD phosphatase catalytic core, and a middle lipin (M-Lip) domain that is conserved in mammalian and mammalian-like lipins. Crystal structures of the M-Lip domain reveal a previously unrecognized protein fold that dimerizes. The isolated M-Lip domain binds membranes both in vitro and in cells through conserved basic and hydrophobic residues. Deletion of the M-Lip domain in lipin 1 reduces PAP activity, membrane association, and oligomerization, alters subcellular localization, diminishes acceleration of adipocyte differentiation, but does not affect transcriptional co-activation. This establishes the M-Lip domain as a dimeric protein fold that binds membranes and is critical for full functionality of mammalian lipins. The middle lipin domain adopts a membrane-binding dimeric protein fold.,Gu W, Gao S, Wang H, Fleming KD, Hoffmann RM, Yang JW, Patel NM, Choi YM, Burke JE, Reue K, Airola MV Nat Commun. 2021 Aug 5;12(1):4718. doi: 10.1038/s41467-021-24929-5. PMID:34354069[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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