7ROY

The structure of the Fem1B:FNIP1 complex

7ROY の概要

• エントリーDOI: 10.2210/pdb7roy/pdb
• 分子名称: Protein fem-1 homolog B, Folliculin-interacting protein 1, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: complex, redox sensor, stress response, signaling protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 177935.54

構造登録者

Gee, C.L.,Mena, E.L.,Manford, A.G.,Rape, M. (登録日: 2021-08-02, 公開日: 2021-10-13, 最終更新日: 2024-05-22)

主引用文献

Manford, A.G.,Mena, E.L.,Shih, K.Y.,Gee, C.L.,McMinimy, R.,Martinez-Gonzalez, B.,Sherriff, R.,Lew, B.,Zoltek, M.,Rodriguez-Perez, F.,Woldesenbet, M.,Kuriyan, J.,Rape, M.
Structural basis and regulation of the reductive stress response.
Cell, 184:5375-5390.e16, 2021

PubMed Abstract: Although oxidative phosphorylation is best known for producing ATP, it also yields reactive oxygen species (ROS) as invariant byproducts. Depletion of ROS below their physiological levels, a phenomenon known as reductive stress, impedes cellular signaling and has been linked to cancer, diabetes, and cardiomyopathy. Cells alleviate reductive stress by ubiquitylating and degrading the mitochondrial gatekeeper FNIP1, yet it is unknown how the responsible E3 ligase CUL2 can bind its target based on redox state and how this is adjusted to changing cellular environments. Here, we show that CUL2 relies on zinc as a molecular glue to selectively recruit reduced FNIP1 during reductive stress. FNIP1 ubiquitylation is gated by pseudosubstrate inhibitors of the BEX family, which prevent premature FNIP1 degradation to protect cells from unwarranted ROS accumulation. FEM1B gain-of-function mutation and BEX deletion elicit similar developmental syndromes, showing that the zinc-dependent reductive stress response must be tightly regulated to maintain cellular and organismal homeostasis.

PubMed: 34562363
DOI: 10.1016/j.cell.2021.09.002

実験手法

X-RAY DIFFRACTION (2.9 Å)