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==Human mitochondrial calcium uniporter (residues 72-189) crystal structure with lithium==
<StructureSection load='5kug' size='340' side='right'caption='[[5kug]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5kug]] is a 1 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=5KUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KUG 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]] 1.9&#8491;</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=5kug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kug OCA], [https://pdbe.org/5kug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kug RCSB], [https://www.ebi.ac.uk/pdbsum/5kug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kug ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MCU_HUMAN MCU_HUMAN] Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria. Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. Activity is regulated by MICU1 and MICU2 that stimulate and inhibit MCU activity, respectively. Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake. Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes.<ref>PMID:21685886</ref> <ref>PMID:21685888</ref> <ref>PMID:22822213</ref> <ref>PMID:22829870</ref> <ref>PMID:22904319</ref> <ref>PMID:23101630</ref> <ref>PMID:23178883</ref> <ref>PMID:24332854</ref> <ref>PMID:24560927</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Calcium (Ca2+) flux into the matrix is tightly controlled by the mitochondrial Ca2+ uniporter (MCU) due to vital roles in cell death and bioenergetics. However, the precise atomic mechanisms of MCU regulation remain unclear. Here, we solved the crystal structure of the N-terminal matrix domain of human MCU, revealing a beta-grasp-like fold with a cluster of negatively charged residues that interacts with divalent cations. Binding of Ca2+ or Mg2+ destabilizes and shifts the self-association equilibrium of the domain toward monomer. Mutational disruption of the acidic face weakens oligomerization of the isolated matrix domain and full-length human protein similar to cation binding and markedly decreases MCU activity. Moreover, mitochondrial Mg2+ loading or blockade of mitochondrial Ca2+ extrusion suppresses MCU Ca2+-uptake rates. Collectively, our data reveal that the beta-grasp-like matrix region harbors an MCU-regulating acidic patch that inhibits human MCU activity in response to Mg2+ and Ca2+ binding.

Structural Insights into Mitochondrial Calcium Uniporter Regulation by Divalent Cations.,Lee SK, Shanmughapriya S, Mok MC, Dong Z, Tomar D, Carvalho E, Rajan S, Junop MS, Madesh M, Stathopulos PB Cell Chem Biol. 2016 Aug 24. pii: S2451-9456(16)30242-2. doi:, 10.1016/j.chembiol.2016.07.012. PMID:27569754<ref>PMID:27569754</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5kug" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mitochondrial calcium uniporter|Mitochondrial calcium uniporter]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Junop MS]]
[[Category: Lee SK]]
[[Category: Mok MCY]]
[[Category: Stathopulos PB]]