4nsc: Difference between revisions

Revision as of 08:36, 18 January 2023

Crystal Structure of CBARA1 in the Apo-form

Structural highlights

4nsc is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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 is a critical event in various cellular activities. Two recently identified proteins, the mitochondrial Ca2+ uniporter (MCU), which is the pore-forming subunit of a Ca2+ channel, and mitochondrial calcium uptake 1 (MICU1), which is the regulator of MCU, are essential in this event. However, the molecular mechanism by which MICU1 regulates MCU remains elusive. In this study, we report the crystal structures of Ca2+-free and Ca2+-bound human MICU1. Our studies reveal that Ca2+-free MICU1 forms a hexamer that binds and inhibits MCU. Upon Ca2+ binding, MICU1 undergoes large conformational changes, resulting in the formation of multiple oligomers to activate MCU. Furthermore, we demonstrate that the affinity of MICU1 for Ca2+ is approximately 15-20 muM. Collectively, our results provide valuable details to decipher the molecular mechanism of MICU1 regulation of mitochondrial calcium uptake.

Structural and mechanistic insights into MICU1 regulation of mitochondrial calcium uptake.,Wang L, Yang X, Li S, Wang Z, Liu Y, Feng J, Zhu Y, Shen Y EMBO J. 2014 Feb 10. PMID:24514027^[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:https://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:https://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:https://dx.doi.org/10.1074/jbc.M112.392084
↑ Wang L, Yang X, Li S, Wang Z, Liu Y, Feng J, Zhu Y, Shen Y. Structural and mechanistic insights into MICU1 regulation of mitochondrial calcium uptake. EMBO J. 2014 Feb 10. PMID:24514027 doi:https://dx.doi.org/10.1002/embj.201386523

Proteopedia Page Contributors and Editors (what is this?)

OCA

[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:https://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:https://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:https://dx.doi.org/10.1074/jbc.M112.392084

[5] Wang L, Yang X, Li S, Wang Z, Liu Y, Feng J, Zhu Y, Shen Y. Structural and mechanistic insights into MICU1 regulation of mitochondrial calcium uptake. EMBO J. 2014 Feb 10. PMID:24514027 doi:https://dx.doi.org/10.1002/embj.201386523

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
 ==Crystal Structure of CBARA1 in the Apo-form==
-<StructureSection load='4nsc' size='340' side='right' caption='[[4nsc]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+<StructureSection load='4nsc' size='340' side='right'caption='[[4nsc]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4nsc]] is a 6 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=4NSC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NSC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4nsc]] is a 6 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=4NSC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NSC FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nsd|4nsd]]</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=4nsc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nsc OCA], [https://pdbe.org/4nsc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nsc RCSB], [https://www.ebi.ac.uk/pdbsum/4nsc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nsc ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MICU1, CALC, CBARA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4nsc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nsc OCA], [http://pdbe.org/4nsc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nsc RCSB], [http://www.ebi.ac.uk/pdbsum/4nsc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nsc 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>
+[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 17: @@
 </div>
 <div class="pdbe-citations 4nsc" 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: Li, S]]
+[[Category: Large Structures]]
-[[Category: Shen, Y]]
+[[Category: Li S]]
-[[Category: Wang, L]]
+[[Category: Shen Y]]
-[[Category: Yang, X]]
+[[Category: Wang L]]
-[[Category: Calcium binding protein]]
+[[Category: Yang X]]
-[[Category: Ef-hand]]

4nsc: Difference between revisions

Revision as of 08:36, 18 January 2023

Crystal Structure of CBARA1 in the Apo-form

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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