8GQZ
Crystal structure of mitochondrial citrate synthase (Cit1) from Saccharomyces cerevisiae
Summary for 8GQZ
| Entry DOI | 10.2210/pdb8gqz/pdb |
| Descriptor | Citrate synthase, SODIUM ION, CHLORIDE ION, ... (6 entities in total) |
| Functional Keywords | tca cycle, mitochondrial protein, citrate metabolism, scfucc1 ubiquitin ligase, proteasome-dependent degradation, transferase |
| Biological source | Saccharomyces cerevisiae (baker's yeast) |
| Total number of polymer chains | 2 |
| Total formula weight | 107240.80 |
| Authors | Nishio, K.,Nakatsukasa, K.,Kamura, T.,Mizushima, T. (deposition date: 2022-08-31, release date: 2023-04-26, Last modification date: 2024-05-29) |
| Primary citation | 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 Cited by 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: 37058555DOI: 10.1126/sciadv.adf1956 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.42 Å) |
Structure validation
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