2n3y
From Proteopedia
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==NMR structure of the Y48pCMF variant of human cytochrome c in its reduced state== | ==NMR structure of the Y48pCMF variant of human cytochrome c in its reduced state== | ||
| - | <StructureSection load='2n3y' size='340' side='right' caption='[[2n3y | + | <StructureSection load='2n3y' size='340' side='right'caption='[[2n3y]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2n3y]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N3Y OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[2n3y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N3Y FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PA:4-(CARBOXYMETHYL)-L-PHENYLALANINE'>1PA</scene>, <scene name='pdbligand=MH0:MESOHEME'>MH0</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2n3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n3y OCA], [https://pdbe.org/2n3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n3y RCSB], [https://www.ebi.ac.uk/pdbsum/2n3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n3y ProSAT]</span></td></tr> |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [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 == | ||
| - | [ | + | [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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Regulation of mitochondrial activity allows cells to adapt to changing conditions and to control oxidative stress, and its dysfunction can lead to hypoxia-dependent pathologies such as ischemia and cancer. Although cytochrome c phosphorylation-in particular, at tyrosine 48-is a key modulator of mitochondrial signaling, its action and molecular basis remain unknown. Here we mimic phosphorylation of cytochrome c by replacing tyrosine 48 with p-carboxy-methyl-l-phenylalanine (pCMF). The NMR structure of the resulting mutant reveals significant conformational shifts and enhanced dynamics around pCMF that could explain changes observed in its functionality: The phosphomimetic mutation impairs cytochrome c diffusion between respiratory complexes, enhances hemeprotein peroxidase and reactive oxygen species scavenging activities, and hinders caspase-dependent apoptosis. Our findings provide a framework to further investigate the modulation of mitochondrial activity by phosphorylated cytochrome c and to develop novel therapeutic approaches based on its prosurvival effects. | ||
| + | |||
| + | Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48.,Moreno-Beltran B, Guerra-Castellano A, Diaz-Quintana A, Del Conte R, Garcia-Maurino SM, Diaz-Moreno S, Gonzalez-Arzola K, Santos-Ocana C, Velazquez-Campoy A, De la Rosa MA, Turano P, Diaz-Moreno I Proc Natl Acad Sci U S A. 2017 Apr 11;114(15):E3041-E3050. doi:, 10.1073/pnas.1618008114. Epub 2017 Mar 27. PMID:28348229<ref>PMID:28348229</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2n3y" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: De la Rosa MA]] |
| - | + | [[Category: Del Conte R]] | |
| - | + | [[Category: Diaz-Moreno I]] | |
| - | [[Category: | + | [[Category: Diaz-Quintana A]] |
| - | [[Category: | + | [[Category: Moreno-Beltran B]] |
| - | [[Category: | + | [[Category: Turano P]] |
| - | [[Category: | + | |
| - | [[Category: | + | |
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Current revision
NMR structure of the Y48pCMF variant of human cytochrome c in its reduced state
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