4ytv

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Crystal structure of Mdm35

Structural highlights

4ytv is a 1 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.45Å
Ligands:CO, GOL
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MDM35_YEAST Involved in mitochondrial distribution and morphology. Mediates the import of UPS1, UPS2 and UPS3, 3 atypical mitochondrial intermembrane space (IMS) proteins lacking the two major IMS-targeting signals, into the intermembrane space.[1] [2] [3]

Publication Abstract from PubMed

Eukaryotic cells are compartmentalized into membrane-bounded organelles whose functions rely on lipid trafficking to achieve membrane-specific compositions of lipids. Here we focused on the Ups1-Mdm35 system, which mediates phosphatidic acid (PA) transfer between the outer and inner mitochondrial membranes, and determined the X-ray structures of Mdm35 and Ups1-Mdm35 with and without PA. The Ups1-Mdm35 complex constitutes a single domain that has a deep pocket and flexible Omega-loop lid. Structure-based mutational analyses revealed that a basic residue at the pocket bottom and the Omega-loop lid are important for PA extraction from the membrane following Ups1 binding. Ups1 binding to the membrane is enhanced by the dissociation of Mdm35. We also show that basic residues around the pocket entrance are important for Ups1 binding to the membrane and PA extraction. These results provide a structural basis for understanding the mechanism of PA transfer between mitochondrial membranes.

Structural and mechanistic insights into phospholipid transfer by Ups1-Mdm35 in mitochondria.,Watanabe Y, Tamura Y, Kawano S, Endo T Nat Commun. 2015 Aug 3;6:7922. doi: 10.1038/ncomms8922. PMID:26235513[4]

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

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Citations
18 reviews cite this structure
Quality control of the mitochondrial proteome.
Song et al. (2021)
17 more
30 other articles
No citations found

References

  1. ↑ Dimmer KS, Fritz S, Fuchs F, Messerschmitt M, Weinbach N, Neupert W, Westermann B. Genetic basis of mitochondrial function and morphology in Saccharomyces cerevisiae. Mol Biol Cell. 2002 Mar;13(3):847-53. PMID:11907266 doi:10.1091/mbc.01-12-0588
  2. ↑ Tamura Y, Iijima M, Sesaki H. Mdm35p imports Ups proteins into the mitochondrial intermembrane space by functional complex formation. EMBO J. 2010 Sep 1;29(17):2875-87. doi: 10.1038/emboj.2010.149. Epub 2010 Jul 9. PMID:20622808 doi:http://dx.doi.org/10.1038/emboj.2010.149
  3. ↑ Potting C, Wilmes C, Engmann T, Osman C, Langer T. Regulation of mitochondrial phospholipids by Ups1/PRELI-like proteins depends on proteolysis and Mdm35. EMBO J. 2010 Sep 1;29(17):2888-98. doi: 10.1038/emboj.2010.169. Epub 2010 Jul 23. PMID:20657548 doi:http://dx.doi.org/10.1038/emboj.2010.169
  4. ↑ Watanabe Y, Tamura Y, Kawano S, Endo T. Structural and mechanistic insights into phospholipid transfer by Ups1-Mdm35 in mitochondria. Nat Commun. 2015 Aug 3;6:7922. doi: 10.1038/ncomms8922. PMID:26235513 doi:http://dx.doi.org/10.1038/ncomms8922

Contents


PDB ID 4ytv

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