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6le5
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the mitochondrial calcium uptake 1 and 2 heterodimer (MICU1-MICU2 heterodimer) in an apo state== | |
| + | <StructureSection load='6le5' size='340' side='right'caption='[[6le5]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6le5]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LE5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6LE5 FirstGlance]. <br> | ||
| + | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MICU1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MICU2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6le5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6le5 OCA], [http://pdbe.org/6le5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6le5 RCSB], [http://www.ebi.ac.uk/pdbsum/6le5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6le5 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/MICU1_HUMAN MICU1_HUMAN]] Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low. Acts as a gatekeeper that senses calcium level via its EF-hand domains and sets a threshold for mitochondrial calcium uptake by MCU, thereby preventing mitochondrial calcium overload. Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake. Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG.<ref>PMID:16002733</ref> <ref>PMID:20693986</ref> <ref>PMID:23101630</ref> <ref>PMID:22904319</ref> [[http://www.uniprot.org/uniprot/MICU2_HUMAN MICU2_HUMAN]] Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:24503055, PubMed:24560927, PubMed:26903221). 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 calcium, avoiding energy dissipation and cell-death triggering (PubMed:24560927).<ref>PMID:24503055</ref> <ref>PMID:24560927</ref> <ref>PMID:26387864</ref> <ref>PMID:26903221</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mitochondrial calcium uptake proteins 1 and 2 (MICU1 and MICU2) mediate mitochondrial Ca(2+) influx via the mitochondrial calcium uniporter (MCU). Its molecular action for Ca(2+) uptake is tightly controlled by the MICU1-MICU2 heterodimer, which comprises Ca(2+) sensing proteins which act as gatekeepers at low [Ca(2+)] or facilitators at high [Ca(2+)]. However, the mechanism underlying the regulation of the Ca(2+) gatekeeping threshold for mitochondrial Ca(2+) uptake through the MCU by the MICU1-MICU2 heterodimer remains unclear. In this study, we determined the crystal structure of the apo form of the human MICU1-MICU2 heterodimer that functions as the MCU gatekeeper. MICU1 and MICU2 assemble in the face-to-face heterodimer with salt bridges and me-thio-nine knobs stabilizing the heterodimer in an apo state. Structural analysis suggests how the heterodimer sets a higher Ca(2+) threshold than the MICU1 homodimer. The structure of the heterodimer in the apo state provides a framework for understanding the gatekeeping role of the MICU1-MICU2 heterodimer. | ||
| - | + | Structure of the MICU1-MICU2 heterodimer provides insights into the gatekeeping threshold shift.,Park J, Lee Y, Park T, Kang JY, Mun SA, Jin M, Yang J, Eom SH IUCrJ. 2020 Feb 27;7(Pt 2):355-365. doi: 10.1107/S2052252520001840. eCollection, 2020 Mar 1. PMID:32148862<ref>PMID:32148862</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6le5" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Eom, S H]] | ||
| + | [[Category: Jin, M]] | ||
| + | [[Category: Kang, J Y]] | ||
[[Category: Lee, Y]] | [[Category: Lee, Y]] | ||
| - | [[Category: Kang, J.Y]] | ||
| - | [[Category: Yang, J]] | ||
| - | [[Category: Eom, S.H]] | ||
| - | [[Category: Park, T]] | ||
[[Category: Park, J]] | [[Category: Park, J]] | ||
| - | [[Category: | + | [[Category: Park, T]] |
| + | [[Category: Yang, J]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Metal binding protein]] | ||
| + | [[Category: Mitochondrial calcium uptake 1 and mitochondrial calcium uptake 2]] | ||
Current revision
Crystal structure of the mitochondrial calcium uptake 1 and 2 heterodimer (MICU1-MICU2 heterodimer) in an apo state
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