View source for 4xtb


==Crystal structure of the N-terminal domain of the human mitochondrial calcium uniporter==
<StructureSection load='4xtb' size='340' side='right'caption='[[4xtb]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xtb]] 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=4XTB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XTB 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]] 1.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=4xtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xtb OCA], [https://pdbe.org/4xtb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xtb RCSB], [https://www.ebi.ac.uk/pdbsum/4xtb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xtb 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 ==
The mitochondrial calcium uniporter (MCU) is responsible for mitochondrial calcium uptake and homeostasis. It is also a target for the regulation of cellular anti-/pro-apoptosis and necrosis by several oncogenes and tumour suppressors. Herein, we report the crystal structure of the MCU N-terminal domain (NTD) at a resolution of 1.50 A in a novel fold and the S92A MCU mutant at 2.75 A resolution; the residue S92 is a predicted CaMKII phosphorylation site. The assembly of the mitochondrial calcium uniporter complex (uniplex) and the interaction with the MCU regulators such as the mitochondrial calcium uptake-1 and mitochondrial calcium uptake-2 proteins (MICU1 and MICU2) are not affected by the deletion of MCU NTD. However, the expression of the S92A mutant or a NTD deletion mutant failed to restore mitochondrial Ca2+ uptake in a stable MCU knockdown HeLa cell line and exerted dominant-negative effects in the wild-type MCU-expressing cell line. These results suggest that the NTD of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation.

Structure and function of the N-terminal domain of the human mitochondrial calcium uniporter.,Lee Y, Min CK, Kim TG, Song HK, Lim Y, Kim D, Shin K, Kang M, Kang JY, Youn HS, Lee JG, An JY, Park KR, Lim JJ, Kim JH, Kim JH, Park ZY, Kim YS, Wang J, Kim DH, Eom SH EMBO Rep. 2015 Sep 3. pii: e201540436. PMID:26341627<ref>PMID:26341627</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4xtb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mitochondrial calcium uniporter|Mitochondrial calcium uniporter]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: An JY]]
[[Category: Eom SH]]
[[Category: Kang JY]]
[[Category: Kang M]]
[[Category: Kim D]]
[[Category: Kim DH]]
[[Category: Kim JH]]
[[Category: Kim TG]]
[[Category: Kim Y-S]]
[[Category: Lee J-G]]
[[Category: Lee Y]]
[[Category: Lim JJ]]
[[Category: Lim Y]]
[[Category: Min CK]]
[[Category: Park KR]]
[[Category: Park ZY]]
[[Category: Shin K]]
[[Category: Song HK]]
[[Category: Wang J]]
[[Category: Youn H-S]]