|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal structure of human SCO1 complexed with nickel.== | | ==Crystal structure of human SCO1 complexed with nickel.== |
| - | <StructureSection load='2ggt' size='340' side='right' caption='[[2ggt]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='2ggt' size='340' side='right'caption='[[2ggt]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ggt]] is a 2 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=2GGT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GGT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ggt]] is a 2 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=2GGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GGT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wp0|1wp0]], [[1on4|1on4]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SCO1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=2ggt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ggt OCA], [https://pdbe.org/2ggt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ggt RCSB], [https://www.ebi.ac.uk/pdbsum/2ggt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ggt 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=2ggt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ggt OCA], [http://pdbe.org/2ggt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ggt RCSB], [http://www.ebi.ac.uk/pdbsum/2ggt PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/SCO1_HUMAN SCO1_HUMAN]] Defects in SCO1 are a cause of mitochondrial complex IV deficiency (MT-C4D) [MIM:[http://omim.org/entry/220110 220110]]; also known as cytochrome c oxidase deficiency. A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, excercise intolerance, developmental delay, delayed motor development and mental retardation. A subset of patients manifest Leigh syndrome.<ref>PMID:17189203</ref> <ref>PMID:11013136</ref> | + | [https://www.uniprot.org/uniprot/SCO1_HUMAN SCO1_HUMAN] Defects in SCO1 are a cause of mitochondrial complex IV deficiency (MT-C4D) [MIM:[https://omim.org/entry/220110 220110]; also known as cytochrome c oxidase deficiency. A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, excercise intolerance, developmental delay, delayed motor development and mental retardation. A subset of patients manifest Leigh syndrome.<ref>PMID:17189203</ref> <ref>PMID:11013136</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SCO1_HUMAN SCO1_HUMAN]] Thought to play a role in cellular copper homeostasis, mitochondrial redox signaling or insertion of copper into the active site of COX.<ref>PMID:17189203</ref> <ref>PMID:15659396</ref> <ref>PMID:16735468</ref> | + | [https://www.uniprot.org/uniprot/SCO1_HUMAN SCO1_HUMAN] Thought to play a role in cellular copper homeostasis, mitochondrial redox signaling or insertion of copper into the active site of COX.<ref>PMID:17189203</ref> <ref>PMID:15659396</ref> <ref>PMID:16735468</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gg/2ggt_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gg/2ggt_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ggt ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| Line 35: |
Line 35: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Banci, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Bertini, I]] | + | [[Category: Banci L]] |
| - | [[Category: Calderone, V]] | + | [[Category: Bertini I]] |
| - | [[Category: Ciofi-Baffoni, S]] | + | [[Category: Calderone V]] |
| - | [[Category: Mangani, S]] | + | [[Category: Ciofi-Baffoni S]] |
| - | [[Category: Martinelli, M]] | + | [[Category: Mangani S]] |
| - | [[Category: Palumaa, P]] | + | [[Category: Martinelli M]] |
| - | [[Category: Wang, S]] | + | [[Category: Palumaa P]] |
| - | [[Category: Chaperone]]
| + | [[Category: Wang S]] |
| - | [[Category: Copper chaperone]]
| + | |
| - | [[Category: Cu-binding protein]]
| + | |
| - | [[Category: Disuplhide]]
| + | |
| - | [[Category: Mitochondrial assembly factor]]
| + | |
| - | [[Category: Mitochondrion]]
| + | |
| - | [[Category: Nickel]]
| + | |
| - | [[Category: Redox]]
| + | |
| Structural highlights
Disease
SCO1_HUMAN Defects in SCO1 are a cause of mitochondrial complex IV deficiency (MT-C4D) [MIM:220110; also known as cytochrome c oxidase deficiency. A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, excercise intolerance, developmental delay, delayed motor development and mental retardation. A subset of patients manifest Leigh syndrome.[1] [2]
Function
SCO1_HUMAN Thought to play a role in cellular copper homeostasis, mitochondrial redox signaling or insertion of copper into the active site of COX.[3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The solution structures of apo, Cu(I), and Ni(II) human Sco1 have been determined. The protein passes from an open and conformationally mobile state to a closed and rigid conformation upon metal binding as shown by electrospray ionization MS and NMR data. The metal ligands of Cu(I) are two Cys residues of the CPXXCP motif and a His residue. The latter is suitably located to coordinate the metal anchored by the two Cys residues. The coordination sphere of Ni(II) in solution is completed by another ligand, possibly Asp. Crystals of the Ni(II) derivative were also obtained with the Ni(II) ion bound to the same His residue and to the two oxidized Cys residues of the CPXXCP motif. We propose that the various structures solved here represent the various states of the protein in its functional cycle and that the metal can be bound to the oxidized protein at a certain stage. Although it now seems reasonable that Sco1, which is characterized by a thioredoxin fold, has evolved to bind a metal atom via the di-Cys motif to act as a copper chaperone, the oxidized form of the nickel-bound protein suggests that it may also maintain the thioredoxin function.
A hint for the function of human Sco1 from different structures.,Banci L, Bertini I, Calderone V, Ciofi-Baffoni S, Mangani S, Martinelli M, Palumaa P, Wang S Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8595-600. Epub 2006 May 30. PMID:16735468[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Leary SC, Cobine PA, Kaufman BA, Guercin GH, Mattman A, Palaty J, Lockitch G, Winge DR, Rustin P, Horvath R, Shoubridge EA. The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. Cell Metab. 2007 Jan;5(1):9-20. PMID:17189203 doi:10.1016/j.cmet.2006.12.001
- ↑ Valnot I, Osmond S, Gigarel N, Mehaye B, Amiel J, Cormier-Daire V, Munnich A, Bonnefont JP, Rustin P, Rotig A. Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy. Am J Hum Genet. 2000 Nov;67(5):1104-9. Epub 2000 Sep 28. PMID:11013136 doi:10.1016/S0002-9297(07)62940-1
- ↑ Leary SC, Cobine PA, Kaufman BA, Guercin GH, Mattman A, Palaty J, Lockitch G, Winge DR, Rustin P, Horvath R, Shoubridge EA. The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. Cell Metab. 2007 Jan;5(1):9-20. PMID:17189203 doi:10.1016/j.cmet.2006.12.001
- ↑ Williams JC, Sue C, Banting GS, Yang H, Glerum DM, Hendrickson WA, Schon EA. Crystal structure of human SCO1: implications for redox signaling by a mitochondrial cytochrome c oxidase "assembly" protein. J Biol Chem. 2005 Apr 15;280(15):15202-11. Epub 2005 Jan 19. PMID:15659396 doi:10.1074/jbc.M410705200
- ↑ Banci L, Bertini I, Calderone V, Ciofi-Baffoni S, Mangani S, Martinelli M, Palumaa P, Wang S. A hint for the function of human Sco1 from different structures. Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8595-600. Epub 2006 May 30. PMID:16735468
- ↑ Banci L, Bertini I, Calderone V, Ciofi-Baffoni S, Mangani S, Martinelli M, Palumaa P, Wang S. A hint for the function of human Sco1 from different structures. Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8595-600. Epub 2006 May 30. PMID:16735468
|
