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6kyl

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Crystal Structure of Phosphatidic acid Transporter Ups1/Mdm35 in Complex with (2R)-3-(phosphonooxy)propane-1,2-diyl dihexanoate

Structural highlights

6kyl is a 4 chain structure with sequence from Saccharomyces cerevisiae S288C. This structure supersedes the now removed PDB entry 5jqo. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.55Å
Ligands:
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

Cardiolipin, an essential mitochondrial physiological regulator, is synthesized from phosphatidic acid (PA) in the inner mitochondrial membrane (IMM). PA is synthesized in the endoplasmic reticulum and transferred to the IMM via the outer mitochondrial membrane (OMM) under mediation by the Ups1/Mdm35 protein family. Despite the availability of numerous crystal structures, the detailed mechanism underlying PA transfer between mitochondrial membranes remains unclear. Here, a model of Ups1/Mdm35-membrane interaction is established using combined crystallographic data, all-atom molecular dynamics simulations, extensive structural comparisons, and biophysical assays. The alpha2-loop, L2-loop, and alpha3 helix of Ups1 mediate membrane interactions. Moreover, non-complexed Ups1 on membranes is found to be a key transition state for PA transfer. The membrane-bound non-complexed Ups1/ membrane-bound Ups1 ratio, which can be regulated by environmental pH, is inversely correlated with the PA transfer activity of Ups1/Mdm35. These results demonstrate a new model of the fine conformational changes of Ups1/Mdm35 during PA transfer.

Molecular mechanism of mitochondrial phosphatidate transfer by Ups1.,Lu J, Chan C, Yu L, Fan J, Sun F, Zhai Y Commun Biol. 2020 Aug 25;3(1):468. doi: 10.1038/s42003-020-01121-x. PMID:32843686^[4]

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

References

↑ 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
↑ 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
↑ 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
↑ Lu J, Chan C, Yu L, Fan J, Sun F, Zhai Y. Molecular mechanism of mitochondrial phosphatidate transfer by Ups1. Commun Biol. 2020 Aug 25;3(1):468. doi: 10.1038/s42003-020-01121-x. PMID:32843686 doi:http://dx.doi.org/10.1038/s42003-020-01121-x

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/6kyl"

@@ Line 3: / Line 3: @@
 <StructureSection load='6kyl' size='340' side='right'caption='[[6kyl]], [[Resolution|resolution]] 3.55&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6kyl]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5jqo 5jqo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KYL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KYL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6kyl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5jqo 5jqo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KYL FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=44E:(2R)-3-(PHOSPHONOOXY)PROPANE-1,2-DIYL+DIHEXANOATE'>44E</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]] 3.55&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MDM35, YKL053C-A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), UPS1, YLR193C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=44E:(2R)-3-(PHOSPHONOOXY)PROPANE-1,2-DIYL+DIHEXANOATE'>44E</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6kyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kyl OCA], [http://pdbe.org/6kyl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kyl RCSB], [http://www.ebi.ac.uk/pdbsum/6kyl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kyl ProSAT]</span></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=6kyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kyl OCA], [https://pdbe.org/6kyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kyl RCSB], [https://www.ebi.ac.uk/pdbsum/6kyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kyl ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/MDM35_YEAST 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.<ref>PMID:11907266</ref> <ref>PMID:20622808</ref> <ref>PMID:20657548</ref>  [[http://www.uniprot.org/uniprot/UPS1_YEAST UPS1_YEAST]] Required for maintenance of normal mitochondrial morphology as well as PCP1-dependent processing of MGM1. With UPS2, controls the level of cardiolipin in mitochondria. Cardiolipin is a unique phospholipid with four fatty acid chains and is present mainly in the mitochondrial inner membrane where it stabilizes the electron transport chain supercomplex between complexes III and IV through direct interaction of their subunits.<ref>PMID:16754953</ref> <ref>PMID:19221197</ref> <ref>PMID:19506038</ref> <ref>PMID:20622808</ref>
+[https://www.uniprot.org/uniprot/MDM35_YEAST 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.<ref>PMID:11907266</ref> <ref>PMID:20622808</ref> <ref>PMID:20657548</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Cardiolipin, an essential mitochondrial physiological regulator, is synthesized from phosphatidic acid (PA) in the inner mitochondrial membrane (IMM). PA is synthesized in the endoplasmic reticulum and transferred to the IMM via the outer mitochondrial membrane (OMM) under mediation by the Ups1/Mdm35 protein family. Despite the availability of numerous crystal structures, the detailed mechanism underlying PA transfer between mitochondrial membranes remains unclear. Here, a model of Ups1/Mdm35-membrane interaction is established using combined crystallographic data, all-atom molecular dynamics simulations, extensive structural comparisons, and biophysical assays. The alpha2-loop, L2-loop, and alpha3 helix of Ups1 mediate membrane interactions. Moreover, non-complexed Ups1 on membranes is found to be a key transition state for PA transfer. The membrane-bound non-complexed Ups1/ membrane-bound Ups1 ratio, which can be regulated by environmental pH, is inversely correlated with the PA transfer activity of Ups1/Mdm35. These results demonstrate a new model of the fine conformational changes of Ups1/Mdm35 during PA transfer.
+Molecular mechanism of mitochondrial phosphatidate transfer by Ups1.,Lu J, Chan C, Yu L, Fan J, Sun F, Zhai Y Commun Biol. 2020 Aug 25;3(1):468. doi: 10.1038/s42003-020-01121-x. PMID:32843686<ref>PMID:32843686</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6kyl" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Baker's yeast]]
 [[Category: Large Structures]]
-[[Category: Chan, K C]]
+[[Category: Saccharomyces cerevisiae S288C]]
-[[Category: Fan, J]]
+[[Category: Chan KC]]
-[[Category: Lu, J]]
+[[Category: Fan J]]
-[[Category: Sun, F]]
+[[Category: Lu J]]
-[[Category: Zhai, Y]]
+[[Category: Sun F]]
-[[Category: Lipid transport]]
+[[Category: Zhai Y]]
-[[Category: Transport protein]]

6kyl

From Proteopedia

Current revision

Crystal Structure of Phosphatidic acid Transporter Ups1/Mdm35 in Complex with (2R)-3-(phosphonooxy)propane-1,2-diyl dihexanoate

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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