EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural insights into GM4951 as a lipid droplet GTPase regulating hepatic lipid metabolism.
ジャーナル・号・ページ	Nat Commun, Vol. 16, Issue 1, Page 11458, Year 2025
掲載日	2025年12月12日
著者	Rishi Raj / Yiao Jiang / Rahul Kumar Jha / Eva Marie Y Moresco / Himanshu Joshi / Zhao Zhang / Bruce Beutler /
PubMed 要旨	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 ...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.
リンク	Nat Commun / PubMed:41387427 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.51 - 3.31 Å
構造データ	49057 9n6d EMDB-49057, PDB-9n6d: Dimeric structure of GM4951 手法: EM (単粒子) / 解像度: 3.03 Å PDB-9n2q: Structure of GDP-bound GM4951 手法: X-RAY DIFFRACTION / 解像度: 2.51 Å PDB-9n2r: Structure of GTP-bound GM4951 手法: X-RAY DIFFRACTION / 解像度: 2.75 Å PDB-9n2s: Structure of GDP-bound GM4951_N86K mutant 手法: X-RAY DIFFRACTION / 解像度: 3.31 Å PDB-9n2t: Structure of GDP-bound GM4951_D125G mutant 手法: X-RAY DIFFRACTION / 解像度: 2.6 Å
化合物	ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP, エネルギー貯蔵分子YM ChemComp-GOL: GLYCEROL ChemComp-HOH: WATER ChemComp-GSP: 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE ChemComp-MG*: Unknown entry
由来	mus musculus (ハツカネズミ)
キーワード	LIPID BINDING PROTEIN / Lipid droplet associated protein / GTPase / N86K mutant GM4951 / D125G mutant GM4951 / Lipid droplet associated protein.