8grf

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

Structural highlights

8grf is a 4 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.53Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CISY2_YEAST Peroxisomal citrate synthase involved in the citrate homeostasis (PubMed:25982115, PubMed:3023912). Catalyzes the condensation of acetyl coenzyme A and oxaloacetate to form citrate (PubMed:25982115, PubMed:3023912). Citrate synthase is the rate-limiting enzyme of the tricarboxylic acid (TCA) cycle (Probable).^[1] ^[2] ^[3]

Publication Abstract from PubMed

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(Ucc1). 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.

Defective import of mitochondrial metabolic enzyme elicits ectopic metabolic stress.,Nishio K, Kawarasaki T, Sugiura Y, Matsumoto S, Konoshima A, Takano Y, Hayashi M, Okumura F, Kamura T, Mizushima T, Nakatsukasa K Sci Adv. 2023 Apr 14;9(15):eadf1956. doi: 10.1126/sciadv.adf1956. Epub 2023 Apr , 14. PMID:37058555^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nakatsukasa K, Nishimura T, Byrne SD, Okamoto M, Takahashi-Nakaguchi A, Chibana H, Okumura F, Kamura T. The Ubiquitin Ligase SCF(Ucc1) Acts as a Metabolic Switch for the Glyoxylate Cycle. Mol Cell. 2015 Jul 2;59(1):22-34. PMID:25982115 doi:10.1016/j.molcel.2015.04.013
↑ Kim KS, Rosenkrantz MS, Guarente L. Saccharomyces cerevisiae contains two functional citrate synthase genes. Mol Cell Biol. 1986 Jun;6(6):1936-42. PMID:3023912
↑ Kim KS, Rosenkrantz MS, Guarente L. Saccharomyces cerevisiae contains two functional citrate synthase genes. Mol Cell Biol. 1986 Jun;6(6):1936-42. PMID:3023912
↑ 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. 2023 Apr 14;9(15):eadf1956. PMID:37058555 doi:10.1126/sciadv.adf1956

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OCA

[1] Nakatsukasa K, Nishimura T, Byrne SD, Okamoto M, Takahashi-Nakaguchi A, Chibana H, Okumura F, Kamura T. The Ubiquitin Ligase SCF(Ucc1) Acts as a Metabolic Switch for the Glyoxylate Cycle. Mol Cell. 2015 Jul 2;59(1):22-34. PMID:25982115 doi:10.1016/j.molcel.2015.04.013

[2] Kim KS, Rosenkrantz MS, Guarente L. Saccharomyces cerevisiae contains two functional citrate synthase genes. Mol Cell Biol. 1986 Jun;6(6):1936-42. PMID:3023912

[3] Kim KS, Rosenkrantz MS, Guarente L. Saccharomyces cerevisiae contains two functional citrate synthase genes. Mol Cell Biol. 1986 Jun;6(6):1936-42. PMID:3023912

[4] 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. 2023 Apr 14;9(15):eadf1956. PMID:37058555 doi:10.1126/sciadv.adf1956

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