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==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]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6le5]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6LE5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=6le5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6le5 OCA], [https://pdbe.org/6le5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6le5 RCSB], [https://www.ebi.ac.uk/pdbsum/6le5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6le5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> 
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6le5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Calcium uptake protein 3D structures|Calcium uptake protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Eom SH]]
[[Category: Jin M]]
[[Category: Kang JY]]
[[Category: Lee Y]]
[[Category: Park J]]
[[Category: Park T]]
[[Category: Yang J]]