6wdo: Difference between revisions

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<StructureSection load='6wdo' size='340' side='right'caption='[[6wdo]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
<StructureSection load='6wdo' size='340' side='right'caption='[[6wdo]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6wdo]] is a 20 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=6WDO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WDO FirstGlance]. <br>
<table><tr><td colspan='2'>[[6wdo]] is a 20 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=6WDO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WDO FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCU, C10orf42, CCDC109A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SMDT1, C22orf32, EMRE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MICU1, CALC, CBARA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MICU2, EFHA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wdo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wdo OCA], [http://pdbe.org/6wdo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wdo RCSB], [http://www.ebi.ac.uk/pdbsum/6wdo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wdo 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=6wdo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wdo OCA], [https://pdbe.org/6wdo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wdo RCSB], [https://www.ebi.ac.uk/pdbsum/6wdo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wdo ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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/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>  [[http://www.uniprot.org/uniprot/EMRE_HUMAN EMRE_HUMAN]] Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria (PubMed:24231807, PubMed:26774479, PubMed:27099988). Required to bridge the calcium-sensing proteins MICU1 and MICU2 with the calcium-conducting subunit MCU (PubMed:24231807). Plays a central role in regulating the uniplex complex response to intracellular calcium signaling (PubMed:27099988). Acts by mediating activation of MCU and retention of MICU1 to the MCU pore, in order to ensure tight regulation of the uniplex complex and appropriate responses to intracellular calcium signaling (PubMed:27099988).<ref>PMID:24231807</ref> <ref>PMID:26774479</ref> <ref>PMID:27099988</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> 
[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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mitochondria take up Ca(2+) through the mitochondrial calcium uniporter complex to regulate energy production, cytosolic Ca(2+) signalling and cell death(1,2). In mammals, the uniporter complex (uniplex) contains four core components: the pore-forming MCU protein, the gatekeepers MICU1 and MICU2, and an auxiliary subunit, EMRE, essential for Ca(2+) transport(3-8). To prevent detrimental Ca(2+) overload, the activity of MCU must be tightly regulated by MICUs, which sense changes in cytosolic Ca(2+) concentrations to switch MCU on and off(9,10). Here we report cryo-electron microscopic structures of the human mitochondrial calcium uniporter holocomplex in inhibited and Ca(2+)-activated states. These structures define the architecture of this multicomponent Ca(2+)-uptake machinery and reveal the gating mechanism by which MICUs control uniporter activity. Our work provides a framework for understanding regulated Ca(2+) uptake in mitochondria, and could suggest ways of modulating uniporter activity to treat diseases related to mitochondrial Ca(2+) overload.


Structure and mechanism of the mitochondrial Ca(2+) uniporter holocomplex.,Fan M, Zhang J, Tsai CW, Orlando BJ, Rodriguez M, Xu Y, Liao M, Tsai MF, Feng L Nature. 2020 Jun;582(7810):129-133. doi: 10.1038/s41586-020-2309-6. Epub 2020 May, 20. PMID:32494073<ref>PMID:32494073</ref>
==See Also==
 
*[[Calcium uptake protein 3D structures|Calcium uptake protein 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
*[[Mitochondrial calcium uniporter|Mitochondrial calcium uniporter]]
</div>
<div class="pdbe-citations 6wdo" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Fan, M]]
[[Category: Fan M]]
[[Category: Feng, L]]
[[Category: Feng L]]
[[Category: Zhang, J]]
[[Category: Zhang J]]
[[Category: Membrane protein]]

Latest revision as of 17:43, 6 March 2024

Cryo-EM structure of mitochondrial calcium uniporter holocomplex in high Ca2+Cryo-EM structure of mitochondrial calcium uniporter holocomplex in high Ca2+

Structural highlights

6wdo is a 20 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.6Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2] [3] [4]

See Also

References

  1. ↑ Aichberger KJ, Mittermann I, Reininger R, Seiberler S, Swoboda I, Spitzauer S, Kopp T, Stingl G, Sperr WR, Valent P, Repa A, Bohle B, Kraft D, Valenta R. Hom s 4, an IgE-reactive autoantigen belonging to a new subfamily of calcium-binding proteins, can induce Th cell type 1-mediated autoreactivity. J Immunol. 2005 Jul 15;175(2):1286-94. PMID:16002733
  2. ↑ Perocchi F, Gohil VM, Girgis HS, Bao XR, McCombs JE, Palmer AE, Mootha VK. MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake. Nature. 2010 Sep 16;467(7313):291-6. doi: 10.1038/nature09358. Epub 2010 Aug 8. PMID:20693986 doi:http://dx.doi.org/10.1038/nature09358
  3. ↑ Mallilankaraman K, Doonan P, Cardenas C, Chandramoorthy HC, Muller M, Miller R, Hoffman NE, Gandhirajan RK, Molgo J, Birnbaum MJ, Rothberg BS, Mak DO, Foskett JK, Madesh M. MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival. Cell. 2012 Oct 26;151(3):630-44. doi: 10.1016/j.cell.2012.10.011. PMID:23101630 doi:http://dx.doi.org/10.1016/j.cell.2012.10.011
  4. ↑ Alam MR, Groschner LN, Parichatikanond W, Kuo L, Bondarenko AI, Rost R, Waldeck-Weiermair M, Malli R, Graier WF. Mitochondrial Ca2+ uptake 1 (MICU1) and mitochondrial ca2+ uniporter (MCU) contribute to metabolism-secretion coupling in clonal pancreatic beta-cells. J Biol Chem. 2012 Oct 5;287(41):34445-54. doi: 10.1074/jbc.M112.392084. Epub 2012, Aug 17. PMID:22904319 doi:http://dx.doi.org/10.1074/jbc.M112.392084

6wdo, resolution 3.60Å

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