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| | ==Solution structure of oxidized human cytochrome c== | | ==Solution structure of oxidized human cytochrome c== |
| - | <StructureSection load='2n9j' size='340' side='right' caption='[[2n9j]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2n9j' size='340' side='right'caption='[[2n9j]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2n9j]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N9J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N9J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2n9j]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N9J FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2n9i|2n9i]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2n9i|2n9i]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYCS, CYC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYCS, CYC ([https://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=2n9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n9j OCA], [http://pdbe.org/2n9j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n9j RCSB], [http://www.ebi.ac.uk/pdbsum/2n9j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n9j 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=2n9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n9j OCA], [https://pdbe.org/2n9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n9j RCSB], [https://www.ebi.ac.uk/pdbsum/2n9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n9j ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CYC_HUMAN CYC_HUMAN]] Defects in CYCS are the cause of thrombocytopenia type 4 (THC4) [MIM:[http://omim.org/entry/612004 612004]]; also known as autosomal dominant thrombocytopenia type 4. Thrombocytopenia is the presence of relatively few platelets in blood. THC4 is a non-syndromic form of thrombocytopenia. Clinical manifestations of thrombocytopenia are absent or mild. THC4 may be caused by dysregulated platelet formation.<ref>PMID:18345000</ref> | + | [[https://www.uniprot.org/uniprot/CYC_HUMAN CYC_HUMAN]] Defects in CYCS are the cause of thrombocytopenia type 4 (THC4) [MIM:[https://omim.org/entry/612004 612004]]; also known as autosomal dominant thrombocytopenia type 4. Thrombocytopenia is the presence of relatively few platelets in blood. THC4 is a non-syndromic form of thrombocytopenia. Clinical manifestations of thrombocytopenia are absent or mild. THC4 may be caused by dysregulated platelet formation.<ref>PMID:18345000</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CYC_HUMAN CYC_HUMAN]] Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain. Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases. | + | [[https://www.uniprot.org/uniprot/CYC_HUMAN CYC_HUMAN]] Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain. Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Imai, M]] | | [[Category: Imai, M]] |
| | [[Category: Inagaki, F]] | | [[Category: Inagaki, F]] |
| Structural highlights
Disease
[CYC_HUMAN] Defects in CYCS are the cause of thrombocytopenia type 4 (THC4) [MIM:612004]; also known as autosomal dominant thrombocytopenia type 4. Thrombocytopenia is the presence of relatively few platelets in blood. THC4 is a non-syndromic form of thrombocytopenia. Clinical manifestations of thrombocytopenia are absent or mild. THC4 may be caused by dysregulated platelet formation.[1]
Function
[CYC_HUMAN] Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain. Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases.
Publication Abstract from PubMed
Redox-dependent changes in the structure and dynamics of human cytochrome c (Cyt c) were investigated by solution NMR. We found significant structural changes in several regions, including residues 23-28 (loop 3), which were further corroborated by chemical shift differences between the reduced and oxidized states of Cyt c. These differences are essential for discriminating redox states in Cyt c by cytochrome c oxidase (CcO) during electron transfer reactions. Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments identified that the region around His33 undergoes conformational exchanges on the mus-ms timescale, indicating significant redox-dependent structural changes. Because His33 is not part of the interaction site for CcO, our data suggest that the dynamic properties of the region, which is far from the interaction site for CcO, contribute to conformational changes during electron transfer to CcO.
Investigation of the redox-dependent modulation of structure and dynamics in human cytochrome c.,Imai M, Saio T, Kumeta H, Uchida T, Inagaki F, Ishimori K Biochem Biophys Res Commun. 2016 Jan 22;469(4):978-84. doi:, 10.1016/j.bbrc.2015.12.079. Epub 2015 Dec 22. PMID:26718409[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Morison IM, Cramer Borde EM, Cheesman EJ, Cheong PL, Holyoake AJ, Fichelson S, Weeks RJ, Lo A, Davies SM, Wilbanks SM, Fagerlund RD, Ludgate MW, da Silva Tatley FM, Coker MS, Bockett NA, Hughes G, Pippig DA, Smith MP, Capron C, Ledgerwood EC. A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia. Nat Genet. 2008 Apr;40(4):387-9. Epub 2008 Mar 16. PMID:18345000 doi:ng.103
- ↑ Imai M, Saio T, Kumeta H, Uchida T, Inagaki F, Ishimori K. Investigation of the redox-dependent modulation of structure and dynamics in human cytochrome c. Biochem Biophys Res Commun. 2016 Jan 22;469(4):978-84. doi:, 10.1016/j.bbrc.2015.12.079. Epub 2015 Dec 22. PMID:26718409 doi:http://dx.doi.org/10.1016/j.bbrc.2015.12.079
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