6le5

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the mitochondrial calcium uptake 1 and 2 heterodimer (MICU1-MICU2 heterodimer) in an apo state

Structural highlights

6le5 is a 8 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:	X-ray diffraction, Resolution 3.1Å
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]

Publication Abstract from PubMed

Mitochondrial calcium uptake proteins 1 and 2 (MICU1 and MICU2) mediate mitochondrial Ca(2+) influx via the mitochondrial calcium uniporter (MCU). Its molecular action for Ca(2+) uptake is tightly controlled by the MICU1-MICU2 heterodimer, which comprises Ca(2+) sensing proteins which act as gatekeepers at low [Ca(2+)] or facilitators at high [Ca(2+)]. However, the mechanism underlying the regulation of the Ca(2+) gatekeeping threshold for mitochondrial Ca(2+) uptake through the MCU by the MICU1-MICU2 heterodimer remains unclear. In this study, we determined the crystal structure of the apo form of the human MICU1-MICU2 heterodimer that functions as the MCU gatekeeper. MICU1 and MICU2 assemble in the face-to-face heterodimer with salt bridges and me-thio-nine knobs stabilizing the heterodimer in an apo state. Structural analysis suggests how the heterodimer sets a higher Ca(2+) threshold than the MICU1 homodimer. The structure of the heterodimer in the apo state provides a framework for understanding the gatekeeping role of the MICU1-MICU2 heterodimer.

Structure of the MICU1-MICU2 heterodimer provides insights into the gatekeeping threshold shift.,Park J, Lee Y, Park T, Kang JY, Mun SA, Jin M, Yang J, Eom SH IUCrJ. 2020 Feb 27;7(Pt 2):355-365. doi: 10.1107/S2052252520001840. eCollection, 2020 Mar 1. PMID:32148862^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ Park J, Lee Y, Park T, Kang JY, Mun SA, Jin M, Yang J, Eom SH. Structure of the MICU1-MICU2 heterodimer provides insights into the gatekeeping threshold shift. IUCrJ. 2020 Feb 27;7(Pt 2):355-365. doi: 10.1107/S2052252520001840. eCollection, 2020 Mar 1. PMID:32148862 doi:http://dx.doi.org/10.1107/S2052252520001840

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6le5"

@@ Line 3: / Line 3: @@
 <StructureSection load='6le5' size='340' side='right'caption='[[6le5]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6le5]] is a 8 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=6LE5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6LE5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6le5]] is a 8 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=6LE5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LE5 FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 3.1&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MICU1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MICU2 ([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=MSE:SELENOMETHIONINE'>MSE</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=6le5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6le5 OCA], [http://pdbe.org/6le5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6le5 RCSB], [http://www.ebi.ac.uk/pdbsum/6le5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6le5 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=6le5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6le5 OCA], [https://pdbe.org/6le5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6le5 RCSB], [https://www.ebi.ac.uk/pdbsum/6le5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6le5 ProSAT]</span></td></tr>
 </table>
 == 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/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 ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6le5" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Calcium uptake protein 3D structures|Calcium uptake protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Eom, S H]]
+[[Category: Eom SH]]
-[[Category: Jin, M]]
+[[Category: Jin M]]
-[[Category: Kang, J Y]]
+[[Category: Kang JY]]
-[[Category: Lee, Y]]
+[[Category: Lee Y]]
-[[Category: Park, J]]
+[[Category: Park J]]
-[[Category: Park, T]]
+[[Category: Park T]]
-[[Category: Yang, J]]
+[[Category: Yang J]]
-[[Category: Complex]]
-[[Category: Metal binding protein]]
-[[Category: Mitochondrial calcium uptake 1 and mitochondrial calcium uptake 2]]

6le5

From Proteopedia

Current revision

Crystal structure of the mitochondrial calcium uptake 1 and 2 heterodimer (MICU1-MICU2 heterodimer) in an apo state

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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