9N2R
Structure of GTP-bound GM4951
Summary for 9N2R
| Entry DOI | 10.2210/pdb9n2r/pdb |
| Descriptor | Interferon inducible GTPase 1C, GLYCEROL, 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | lipid droplet associated protein, gtpase, lipid binding protein |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 6 |
| Total formula weight | 296222.79 |
| Authors | |
| Primary citation | Raj, R.,Jiang, Y.,Jha, R.K.,Moresco, E.M.Y.,Joshi, H.,Zhang, Z.,Beutler, B. Structural insights into GM4951 as a lipid droplet GTPase regulating hepatic lipid metabolism. Nat Commun, 16:11458-11458, 2025 Cited by PubMed Abstract: 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 GTPγS- 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. PubMed: 41387427DOI: 10.1038/s41467-025-66253-2 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.75 Å) |
Structure validation
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