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8gqz

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Crystal structure of mitochondrial citrate synthase (Cit1) from Saccharomyces cerevisiae

Structural highlights

8gqz is a 2 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 1.42Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CISY1_YEAST Specific citrate synthase with catalytic activity only with acetyl-CoA.^[1] ^[2]

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^[3]

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

References

↑ Graybill ER, Rouhier MF, Kirby CE, Hawes JW. Functional comparison of citrate synthase isoforms from S. cerevisiae. Arch Biochem Biophys. 2007 Sep 1;465(1):26-37. PMID:17570335 doi:10.1016/j.abb.2007.04.039
↑ Guo X, Niemi NM, Hutchins PD, Condon SGF, Jochem A, Ulbrich A, Higbee AJ, Russell JD, Senes A, Coon JJ, Pagliarini DJ. Ptc7p Dephosphorylates Select Mitochondrial Proteins to Enhance Metabolic Function. Cell Rep. 2017 Jan 10;18(2):307-313. PMID:28076776 doi:10.1016/j.celrep.2016.12.049
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8gqz"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8gqz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GQZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GQZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.42&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8gqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gqz OCA], [https://pdbe.org/8gqz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gqz RCSB], [https://www.ebi.ac.uk/pdbsum/8gqz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gqz ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/A0A6A5Q7J3_YEASX A0A6A5Q7J3_YEASX]
+[https://www.uniprot.org/uniprot/CISY1_YEAST CISY1_YEAST] Specific citrate synthase with catalytic activity only with acetyl-CoA.<ref>PMID:17570335</ref> <ref>PMID:28076776</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

8gqz

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Current revision

Crystal structure of mitochondrial citrate synthase (Cit1) from Saccharomyces cerevisiae

Structural highlights

Function

Publication Abstract from PubMed

References

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