9KV7

Cryo-EM structure of mouse RIPK1-DD filament

9KV7 の概要

• エントリーDOI: 10.2210/pdb9kv7/pdb
• EMDBエントリー: 62587
• 分子名称: Receptor-interacting serine/threonine-protein kinase 1 (1 entity in total)
• 機能のキーワード: ripk1, death domain, 568-656, dimerization, immune system
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 23
• 化学式量合計: 317645.41

構造登録者

Zhang, H. (登録日: 2024-12-04, 公開日: 2025-10-15)

主引用文献

Chen, Z.,Gu, X.,Chen, H.,Zhang, H.,Liu, J.,Yang, X.,Cai, Y.,Zhang, M.,Yan, L.,Yang, Y.,Shan, B.,Zhu, Z.J.,Zhang, Y.,Gu, J.,Xu, D.
RIPK1 senses S-adenosylmethionine scarcity to drive cell death and inflammation.
Cell Metab., 37:1732-1749.e9, 2025

PubMed Abstract: The capacity of cells to sense and respond to nutrient availability is essential for metabolic homeostasis. Failure in this process may cause cell death and associated diseases. While nutrient sensing in metabolic pathways is well understood, the mechanisms linking nutrient signals to cell death remain unclear. Here, we show that RIPK1, a key mediator of cell death and inflammation, senses methionine and its metabolite, S-adenosylmethionine (SAM), to dictate cell survival and death. SAM-mediated symmetrical dimethylation at RIPK1 Arg606 by PRMT5 functions as a physiological protective brake against RIPK1 activation. Metabolic perturbations, such as methionine restriction or disrupted one-carbon flux, reduce SAM levels and unmask Arg606, promoting RIPK1 self-association and trans-activation, thereby triggering apoptosis and inflammation. Thus, RIPK1 is a physiological SAM sensor linking methionine and one-carbon metabolism to the control of life-or-death decisions. Our findings suggest that RIPK1 could be a potential target for diseases associated with disrupted SAM availability.

PubMed: 40570842
DOI: 10.1016/j.cmet.2025.05.014

実験手法

ELECTRON MICROSCOPY (3.02 Å)