5c0z: Difference between revisions

<StructureSection load='5c0z' size='340' side='right' caption='[[5c0z]], [[Resolution|resolution]] 1.12&Aring;' scene=''>

<table><tr><td colspan='2'>[[5c0z]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C0Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C0Z FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FC6:HEXACYANOFERRATE(3-)'>FC6</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</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=5c0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c0z OCA], [http://pdbe.org/5c0z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c0z RCSB], [http://www.ebi.ac.uk/pdbsum/5c0z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5c0z ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/CYC_RAT CYC_RAT]] 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 (By similarity).  

Mammalian cytochrome c (Cytc) transfers electrons from the bc(1) complex to cytochrome c oxidase (CcO) as part of the mitochondrial electron transport chain, and it also participates in type II apoptosis. Our recent discovery of two tyrosine phosphorylation sites in Cytc, Tyr97 in bovine heart and Tyr48 in bovine liver, indicates that Cytc functions are regulated through cell signaling. To characterize the role of Cytc tyrosine phosphorylation in detail using an independent approach, we here overexpressed and purified a Tyr48Glu mutant Cytc, mimicking the in vivo Tyr48 phosphorylation found in cow liver, along with wild-type and Tyr48Phe variants as controls. The midpoint redox potential of the phosphomimetic mutant was decreased by 45 mV compared to control (192 vs 237 mV). Similar to Tyr48 in vivo phosphorylated Cytc, direct kinetic analysis of the Cytc reaction with isolated CcO revealed decreased V(max) for the Tyr48Glu mutant by 30% compared to wild type or the Tyr48Phe variants. Moreover, the phosphomimetic substitution resulted in major changes of Cytc functions related to apoptosis. The binding affinity of Tyr48Glu Cytc to cardiolipin was decreased by about 30% compared to wild type or the Tyr48Phe variants, and Cytc peroxidase activity of the Tyr48Glu mutant was cardiolipin-inducible only at high cardiolipin concentration, unlike controls. Importantly, the Tyr48Glu Cytc failed to induce any detectable downstream activation of caspase-3. Our data suggest that in vivo Tyr48 phosphorylation might serve as an antiapoptotic switch and highlight the strategic position and role of the conserved Cytc residue Tyr48 in regulating multiple functions of Cytc.

Phosphomimetic substitution of cytochrome C tyrosine 48 decreases respiration and binding to cardiolipin and abolishes ability to trigger downstream caspase activation.,Pecina P, Borisenko GG, Belikova NA, Tyurina YY, Pecinova A, Lee I, Samhan-Arias AK, Przyklenk K, Kagan VE, Huttemann M Biochemistry. 2010 Aug 10;49(31):6705-14. doi: 10.1021/bi100486s. PMID:20586425<ref>PMID:20586425</ref>

[[Category: Brunzelle, J S]]

[[Category: Edwards, B F.P]]

[[Category: Huttemann, M]]

[[Category: Mahapatra, G]]

[[Category: Vaishnav, A A]]

[[Category: Cytochrome oxidized rat native]]

[[Category: Electron transport]]