View source for 7kih


==Crystal structure of the mouse lipin-1 M-Lip domain==
<StructureSection load='7kih' size='340' side='right'caption='[[7kih]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kih]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KIH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.467&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7kih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kih OCA], [https://pdbe.org/7kih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kih RCSB], [https://www.ebi.ac.uk/pdbsum/7kih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kih ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/LPIN1_MOUSE LPIN1_MOUSE] Defects in Lpin1 are the cause of the fatty liver dystrophy phenotype (fld). Fld mutant mices are characterized by neonatal fatty liver and hypertriglyceridemia that resolve at weaning, and neuropathy affecting peripheral nerve in adulthood. Adipose tissue deficiency, glucose intolerance and increased susceptibility to atherosclerosis are associated with this mutation too. Two independent mutant alleles are characterized in this phenotype, fld and fld2j.
== Function ==
[https://www.uniprot.org/uniprot/LPIN1_MOUSE LPIN1_MOUSE] Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis and therefore controls the metabolism of fatty acids at different levels (PubMed:17158099). Acts also as nuclear transcriptional coactivator for PPARGC1A/PPARA regulatory pathway to modulate lipid metabolism gene expression. Is involved in adipocyte differentiation. Isoform 1 is recruited at the mitochondrion outer membrane and is involved in mitochondrial fission by converting phosphatidic acid to diacylglycerol.<ref>PMID:16950137</ref> <ref>PMID:17158099</ref> 
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== Publication Abstract from PubMed ==
Phospholipid 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<ref>PMID:34354069</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Airola MV]]
[[Category: Gu W]]