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| | <StructureSection load='6eaz' size='340' side='right'caption='[[6eaz]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='6eaz' size='340' side='right'caption='[[6eaz]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6eaz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EAZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EAZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6eaz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EAZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EAZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.504Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Micu2, Efha1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6eaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eaz OCA], [http://pdbe.org/6eaz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eaz RCSB], [http://www.ebi.ac.uk/pdbsum/6eaz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eaz 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=6eaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eaz OCA], [https://pdbe.org/6eaz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eaz RCSB], [https://www.ebi.ac.uk/pdbsum/6eaz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eaz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MICU2_MOUSE MICU2_MOUSE]] Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:23409044, PubMed:24560927). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate and inhibit MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU2 acts as a gatekeeper of MCU that senses calcium level via its EF-hand domains: prevents channel opening at resting Ca(2+), avoiding energy dissipation and cell-death triggering (PubMed:24560927).<ref>PMID:23409044</ref> <ref>PMID:24560927</ref> | + | [https://www.uniprot.org/uniprot/MICU2_MOUSE MICU2_MOUSE] Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:23409044, PubMed:24560927). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate and inhibit MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU2 acts as a gatekeeper of MCU that senses calcium level via its EF-hand domains: prevents channel opening at resting Ca(2+), avoiding energy dissipation and cell-death triggering (PubMed:24560927).<ref>PMID:23409044</ref> <ref>PMID:24560927</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The mitochondrial uniporter is a Ca(2+)-channel complex resident within the organelle's inner membrane. In mammalian cells the uniporter's activity is regulated by Ca(2+) due to concerted action of MICU1 and MICU2, two paralogous, but functionally distinct, EF-hand Ca(2+)-binding proteins. Here we present the X-ray structure of the apo form of Mus musculus MICU2 at 2.5-A resolution. The core structure of MICU2 is very similar to that of MICU1. It consists of two lobes, each containing one canonical Ca(2+)-binding EF-hand (EF1, EF4) and one structural EF-hand (EF2, EF3). Two molecules of MICU2 form a symmetrical dimer stabilized by highly conserved hydrophobic contacts between exposed residues of EF1 of one monomer and EF3 of another. Similar interactions stabilize MICU1 dimers, allowing exchange between homo- and heterodimers. The tight EF1-EF3 interface likely accounts for the structural and functional coupling between the Ca(2+)-binding sites in MICU1, MICU2, and their complex that leads to the previously reported Ca(2+)-binding cooperativity and dominant negative effect of mutation of the Ca(2+)-binding sites in either protein. The N- and C-terminal segments of the two proteins are distinctly different. In MICU2 the C-terminal helix is significantly longer than in MICU1, and it adopts a more rigid structure. MICU2's C-terminal helix is dispensable in vitro for its interaction with MICU1 but required for MICU2's function in cells. We propose that in the MICU1-MICU2 oligomeric complex the C-terminal helices of both proteins form a central semiautonomous assembly which contributes to the gating mechanism of the uniporter.
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| - | | + | |
| - | Crystal structure of MICU2 and comparison with MICU1 reveal insights into the uniporter gating mechanism.,Kamer KJ, Jiang W, Kaushik VK, Mootha VK, Grabarek Z Proc Natl Acad Sci U S A. 2019 Feb 12. pii: 1817759116. doi:, 10.1073/pnas.1817759116. PMID:30755530<ref>PMID:30755530</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6eaz" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Calcium uptake protein 3D structures|Calcium uptake protein 3D structures]] | | *[[Calcium uptake protein 3D structures|Calcium uptake protein 3D structures]] |
| | + | *[[Mitochondrial calcium uniporter|Mitochondrial calcium uniporter]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Grabarek, Z]] | + | [[Category: Grabarek Z]] |
| - | [[Category: Kamer, K J]] | + | [[Category: Kamer KJ]] |
| - | [[Category: Calcium]]
| + | |
| - | [[Category: Channel]]
| + | |
| - | [[Category: Ef hand]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Mitochondria]]
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| - | [[Category: Uniporter]]
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| Structural highlights
Function
MICU2_MOUSE Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:23409044, PubMed:24560927). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate and inhibit MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU2 acts as a gatekeeper of MCU that senses calcium level via its EF-hand domains: prevents channel opening at resting Ca(2+), avoiding energy dissipation and cell-death triggering (PubMed:24560927).[1] [2]
See Also
References
- ↑ Plovanich M, Bogorad RL, Sancak Y, Kamer KJ, Strittmatter L, Li AA, Girgis HS, Kuchimanchi S, De Groot J, Speciner L, Taneja N, Oshea J, Koteliansky V, Mootha VK. MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling. PLoS One. 2013;8(2):e55785. doi: 10.1371/journal.pone.0055785. Epub 2013 Feb 7. PMID:23409044 doi:http://dx.doi.org/10.1371/journal.pone.0055785
- ↑ Patron M, Checchetto V, Raffaello A, Teardo E, Vecellio Reane D, Mantoan M, Granatiero V, Szabo I, De Stefani D, Rizzuto R. MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol Cell. 2014 Mar 6;53(5):726-37. doi: 10.1016/j.molcel.2014.01.013. Epub 2014, Feb 20. PMID:24560927 doi:http://dx.doi.org/10.1016/j.molcel.2014.01.013
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