8GRF

Crystal structure of F-box protein in the ternary complex with adaptor protein Skp1(DL) and its substrate

8GRF の概要

• エントリーDOI: 10.2210/pdb8grf/pdb
• 関連するPDBエントリー: 8GQZ
• 分子名称: Citrate synthase, F-box protein UCC1, E3 ubiquitin ligase complex SCF subunit, ... (5 entities in total)
• 機能のキーワード: f-box protein, glyoxylate cycle, e3 ubiquitin ligase, transferase, transferase-ligase complex, transferase/ligase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 168759.04

構造登録者

Nishio, K.,Nakatsukasa, K.,Kamura, T.,Mizushima, T. (登録日: 2022-09-01, 公開日: 2023-04-26, 最終更新日: 2024-05-29)

主引用文献

Nishio, K.,Kawarasaki, T.,Sugiura, Y.,Matsumoto, S.,Konoshima, A.,Takano, Y.,Hayashi, M.,Okumura, F.,Kamura, T.,Mizushima, T.,Nakatsukasa, K.
Defective import of mitochondrial metabolic enzyme elicits ectopic metabolic stress.
Sci Adv, 9:eadf1956-eadf1956, 2023

PubMed Abstract: Deficiencies in mitochondrial protein import are associated with a number of diseases. However, although nonimported mitochondrial proteins are at great risk of aggregation, it remains largely unclear how their accumulation causes cell dysfunction. Here, we show that nonimported citrate synthase is targeted for proteasomal degradation by the ubiquitin ligase SCF. Unexpectedly, our structural and genetic analyses revealed that nonimported citrate synthase appears to form an enzymatically active conformation in the cytosol. Its excess accumulation caused ectopic citrate synthesis, which, in turn, led to an imbalance in carbon flux of sugar, a reduction of the pool of amino acids and nucleotides, and a growth defect. Under these conditions, translation repression is induced and acts as a protective mechanism that mitigates the growth defect. We propose that the consequence of mitochondrial import failure is not limited to proteotoxic insults, but that the accumulation of a nonimported metabolic enzyme elicits ectopic metabolic stress.

PubMed: 37058555
DOI: 10.1126/sciadv.adf1956

実験手法

X-RAY DIFFRACTION (2.53 Å)