9N6D

Dimeric structure of GM4951

9N6D の概要

• エントリーDOI: 10.2210/pdb9n6d/pdb
• EMDBエントリー: 49057
• 分子名称: Interferon inducible GTPase 1C (1 entity in total)
• 機能のキーワード: lipid droplet associated protein., lipid binding protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 97124.37

構造登録者

Raj, R.,Beutler, B. (登録日: 2025-02-05, 公開日: 2026-01-14)

主引用文献

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

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: 41387427
DOI: 10.1038/s41467-025-66253-2

実験手法

ELECTRON MICROSCOPY (3.03 Å)