9n2s: Difference between revisions
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==Structure of GDP-bound GM4951_N86K mutant== | |||
<StructureSection load='9n2s' size='340' side='right'caption='[[9n2s]], [[Resolution|resolution]] 3.31Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9n2s]] is a 2 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=9N2S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9N2S 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]] 3.31Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></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=9n2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9n2s OCA], [https://pdbe.org/9n2s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9n2s RCSB], [https://www.ebi.ac.uk/pdbsum/9n2s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9n2s ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q3UED7_MOUSE Q3UED7_MOUSE] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
GM4951 is an immunity-related GTPase (IRG) that counteracts hepatic lipid accumulation in mice fed a high-fat diet. We determine full-length protein structures of GTPgammaS- and GDP-bound GM4951, and two missense mutants (N86K or D125G) associated with metabolic dysfunction-associated steatotic liver disease (MASLD) in mice. All four structures reveal a conserved GTPase domain fold and a helix bundle composed of the N- and C-terminal regions. Each mutation alters the dynamics of the switch-I and switch-II loops important for catalytic function and lipid droplet (LD) localization. GM4951 predominantly forms dimers in vitro. Cryo-electron microscopy reveals a dimer interface formed by the helical domains of two protomers (tail to tail), distinct from other IRGs. The N-terminal helices are necessary for LD localization, while a disulfide bond between helices in the GTPase domain and C-terminus is necessary for interaction with MASLD-associated HSD17B13. Distinct N- and C-terminal conformations set GM4951 apart from other IRGs structurally and functionally. | |||
Structural insights into GM4951 as a lipid droplet GTPase regulating hepatic lipid metabolism.,Raj R, Jiang Y, Jha RK, Moresco EMY, Joshi H, Zhang Z, Beutler B Nat Commun. 2025 Dec 12;16(1):11458. doi: 10.1038/s41467-025-66253-2. PMID:41387427<ref>PMID:41387427</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9n2s" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Beutler B]] | |||
[[Category: Raj R]] | |||
Latest revision as of 09:20, 14 January 2026
Structure of GDP-bound GM4951_N86K mutant
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