6eaz: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(One intermediate revision by the same user not shown)
Line 3: Line 3:
<StructureSection load='6eaz' size='340' side='right'caption='[[6eaz]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='6eaz' size='340' side='right'caption='[[6eaz]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6eaz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EAZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EAZ FirstGlance]. <br>
<table><tr><td colspan='2'>[[6eaz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EAZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EAZ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.504&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Micu2, Efha1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=6eaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eaz OCA], [http://pdbe.org/6eaz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eaz RCSB], [http://www.ebi.ac.uk/pdbsum/6eaz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eaz 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=6eaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eaz OCA], [https://pdbe.org/6eaz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eaz RCSB], [https://www.ebi.ac.uk/pdbsum/6eaz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eaz ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/MICU2_MOUSE MICU2_MOUSE]] Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:23409044, PubMed:24560927). 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 Ca(2+), avoiding energy dissipation and cell-death triggering (PubMed:24560927).<ref>PMID:23409044</ref> <ref>PMID:24560927</ref>
[https://www.uniprot.org/uniprot/MICU2_MOUSE MICU2_MOUSE] Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:23409044, PubMed:24560927). 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 Ca(2+), avoiding energy dissipation and cell-death triggering (PubMed:24560927).<ref>PMID:23409044</ref> <ref>PMID:24560927</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The mitochondrial uniporter is a Ca(2+)-channel complex resident within the organelle's inner membrane. In mammalian cells the uniporter's activity is regulated by Ca(2+) due to concerted action of MICU1 and MICU2, two paralogous, but functionally distinct, EF-hand Ca(2+)-binding proteins. Here we present the X-ray structure of the apo form of Mus musculus MICU2 at 2.5-A resolution. The core structure of MICU2 is very similar to that of MICU1. It consists of two lobes, each containing one canonical Ca(2+)-binding EF-hand (EF1, EF4) and one structural EF-hand (EF2, EF3). Two molecules of MICU2 form a symmetrical dimer stabilized by highly conserved hydrophobic contacts between exposed residues of EF1 of one monomer and EF3 of another. Similar interactions stabilize MICU1 dimers, allowing exchange between homo- and heterodimers. The tight EF1-EF3 interface likely accounts for the structural and functional coupling between the Ca(2+)-binding sites in MICU1, MICU2, and their complex that leads to the previously reported Ca(2+)-binding cooperativity and dominant negative effect of mutation of the Ca(2+)-binding sites in either protein. The N- and C-terminal segments of the two proteins are distinctly different. In MICU2 the C-terminal helix is significantly longer than in MICU1, and it adopts a more rigid structure. MICU2's C-terminal helix is dispensable in vitro for its interaction with MICU1 but required for MICU2's function in cells. We propose that in the MICU1-MICU2 oligomeric complex the C-terminal helices of both proteins form a central semiautonomous assembly which contributes to the gating mechanism of the uniporter.


Crystal structure of MICU2 and comparison with MICU1 reveal insights into the uniporter gating mechanism.,Kamer KJ, Jiang W, Kaushik VK, Mootha VK, Grabarek Z Proc Natl Acad Sci U S A. 2019 Feb 12. pii: 1817759116. doi:, 10.1073/pnas.1817759116. PMID:30755530<ref>PMID:30755530</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 6eaz" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
Line 24: Line 19:
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: Grabarek, Z]]
[[Category: Grabarek Z]]
[[Category: Kamer, K J]]
[[Category: Kamer KJ]]
[[Category: Calcium]]
[[Category: Channel]]
[[Category: Ef hand]]
[[Category: Metal binding protein]]
[[Category: Mitochondria]]
[[Category: Uniporter]]

Latest revision as of 17:40, 13 March 2024

Apo structure of the mitochondrial calcium uniporter protein MICU2Apo structure of the mitochondrial calcium uniporter protein MICU2

Structural highlights

6eaz is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.504Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MICU2_MOUSE Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:23409044, PubMed:24560927). 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 Ca(2+), avoiding energy dissipation and cell-death triggering (PubMed:24560927).[1] [2]

See Also

References

  1. ↑ Plovanich M, Bogorad RL, Sancak Y, Kamer KJ, Strittmatter L, Li AA, Girgis HS, Kuchimanchi S, De Groot J, Speciner L, Taneja N, Oshea J, Koteliansky V, Mootha VK. MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling. PLoS One. 2013;8(2):e55785. doi: 10.1371/journal.pone.0055785. Epub 2013 Feb 7. PMID:23409044 doi:http://dx.doi.org/10.1371/journal.pone.0055785
  2. ↑ Patron M, Checchetto V, Raffaello A, Teardo E, Vecellio Reane D, Mantoan M, Granatiero V, Szabo I, De Stefani D, Rizzuto R. MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol Cell. 2014 Mar 6;53(5):726-37. doi: 10.1016/j.molcel.2014.01.013. Epub 2014, Feb 20. PMID:24560927 doi:http://dx.doi.org/10.1016/j.molcel.2014.01.013

6eaz, resolution 2.50Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=6eaz&oldid=4091829"