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| | ==Solution structure of the pore-forming region of C. elegans Mitochondrial Calcium Uniporter (MCU)== | | ==Solution structure of the pore-forming region of C. elegans Mitochondrial Calcium Uniporter (MCU)== |
| - | <StructureSection load='5id3' size='340' side='right'caption='[[5id3]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='5id3' size='340' side='right'caption='[[5id3]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5id3]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ID3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ID3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5id3]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ID3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ID3 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mcu-1, CELE_K02B2.3, K02B2.3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL])</td></tr> | + | </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=5id3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5id3 OCA], [https://pdbe.org/5id3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5id3 RCSB], [https://www.ebi.ac.uk/pdbsum/5id3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5id3 ProSAT]</span></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=5id3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5id3 OCA], [http://pdbe.org/5id3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5id3 RCSB], [http://www.ebi.ac.uk/pdbsum/5id3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5id3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MCU_CAEEL MCU_CAEEL] Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria (PubMed:25313960, PubMed:31983639). Constitutes a pore-forming and calcium-conducting subunit (By similarity). Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways (By similarity). Required for rapid mitochondrial calcium uptake and mitochondrial reactive oxygen species (mtROS) production after wounding (PubMed:25313960). In addition, together with mitochondrial calcium regulator micu-1, required for mitochondrial calcium uptake following axon injury in PLM touch receptor neurons (PubMed:31983639).[UniProtKB:Q8NE86]<ref>PMID:25313960</ref> <ref>PMID:31983639</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5id3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5id3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Mitochondrial calcium uniporter|Mitochondrial calcium uniporter]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Caeel]] | + | [[Category: Caenorhabditis elegans]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cao, C]] | + | [[Category: Cao C]] |
| - | [[Category: Chou, J J]] | + | [[Category: Chou JJ]] |
| - | [[Category: Cong, Y]] | + | [[Category: Cong Y]] |
| - | [[Category: Cui, T]] | + | [[Category: Cui T]] |
| - | [[Category: Dong, Y]] | + | [[Category: Dong Y]] |
| - | [[Category: Grabarek, Z]] | + | [[Category: Grabarek Z]] |
| - | [[Category: Kong, L]] | + | [[Category: Kong L]] |
| - | [[Category: Liu, Z]] | + | [[Category: Liu Z]] |
| - | [[Category: MPSbyNMR, Membrane Protein Structures by Solution NMR]]
| + | [[Category: Markhard AL]] |
| - | [[Category: Markhard, A L]] | + | [[Category: Mootha VK]] |
| - | [[Category: Mootha, V K]] | + | [[Category: Ouyang B]] |
| - | [[Category: Ouyang, B]] | + | [[Category: Oxenoid K]] |
| - | [[Category: Oxenoid, K]] | + | [[Category: Sancak Y]] |
| - | [[Category: Sancak, Y]] | + | |
| - | [[Category: Calcium channel]]
| + | |
| - | [[Category: Membrane protein structures by solution nmr]]
| + | |
| - | [[Category: Mitochondria]]
| + | |
| - | [[Category: Mpsbynmr]]
| + | |
| - | [[Category: N-terminal domain truncation]]
| + | |
| - | [[Category: Pentamer]]
| + | |
| - | [[Category: Psi-biology]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
MCU_CAEEL Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria (PubMed:25313960, PubMed:31983639). Constitutes a pore-forming and calcium-conducting subunit (By similarity). Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways (By similarity). Required for rapid mitochondrial calcium uptake and mitochondrial reactive oxygen species (mtROS) production after wounding (PubMed:25313960). In addition, together with mitochondrial calcium regulator micu-1, required for mitochondrial calcium uptake following axon injury in PLM touch receptor neurons (PubMed:31983639).[UniProtKB:Q8NE86][1] [2]
Publication Abstract from PubMed
Mitochondria from many eukaryotic clades take up large amounts of calcium (Ca(2+)) via an inner membrane transporter called the uniporter. Transport by the uniporter is membrane potential dependent and sensitive to ruthenium red or its derivative Ru360 (ref. 1). Electrophysiological studies have shown that the uniporter is an ion channel with remarkably high conductance and selectivity. Ca(2+) entry into mitochondria is also known to activate the tricarboxylic acid cycle and seems to be crucial for matching the production of ATP in mitochondria with its cytosolic demand. Mitochondrial calcium uniporter (MCU) is the pore-forming and Ca(2+)-conducting subunit of the uniporter holocomplex, but its primary sequence does not resemble any calcium channel studied to date. Here we report the structure of the pore domain of MCU from Caenorhabditis elegans, determined using nuclear magnetic resonance (NMR) and electron microscopy (EM). MCU is a homo-oligomer in which the second transmembrane helix forms a hydrophilic pore across the membrane. The channel assembly represents a new solution of ion channel architecture, and is stabilized by a coiled-coil motif protruding into the mitochondrial matrix. The critical DXXE motif forms the pore entrance, which features two carboxylate rings; based on the ring dimensions and functional mutagenesis, these rings appear to form the selectivity filter. To our knowledge, this is one of the largest membrane protein structures characterized by NMR, and provides a structural blueprint for understanding the function of this channel.
Architecture of the mitochondrial calcium uniporter.,Oxenoid K, Dong Y, Cao C, Cui T, Sancak Y, Markhard AL, Grabarek Z, Kong L, Liu Z, Ouyang B, Cong Y, Mootha VK, Chou JJ Nature. 2016 May 2;533(7602):269-73. doi: 10.1038/nature17656. PMID:27135929[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Xu S, Chisholm AD. C. elegans epidermal wounding induces a mitochondrial ROS burst that promotes wound repair. Dev Cell. 2014 Oct 13;31(1):48-60. PMID:25313960 doi:10.1016/j.devcel.2014.08.002
- ↑ Tang NH, Kim KW, Xu S, Blazie SM, Yee BA, Yeo GW, Jin Y, Chisholm AD. The mRNA Decay Factor CAR-1/LSM14 Regulates Axon Regeneration via Mitochondrial Calcium Dynamics. Curr Biol. 2020 Mar 9;30(5):865-876.e7. PMID:31983639 doi:10.1016/j.cub.2019.12.061
- ↑ Oxenoid K, Dong Y, Cao C, Cui T, Sancak Y, Markhard AL, Grabarek Z, Kong L, Liu Z, Ouyang B, Cong Y, Mootha VK, Chou JJ. Architecture of the mitochondrial calcium uniporter. Nature. 2016 May 2;533(7602):269-73. doi: 10.1038/nature17656. PMID:27135929 doi:http://dx.doi.org/10.1038/nature17656
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