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2n3y

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Revision as of 07:56, 4 November 2020

NMR structure of the Y48pCMF variant of human cytochrome c in its reduced state

Structural highlights

2n3y is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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^[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
↑ 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. Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48. 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 doi:http://dx.doi.org/10.1073/pnas.1618008114

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2n3y"

@@ Line 1: / Line 1: @@
 ==NMR structure of the Y48pCMF variant of human cytochrome c in its reduced state==
-<StructureSection load='2n3y' size='340' side='right' caption='[[2n3y]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2n3y' size='340' side='right'caption='[[2n3y]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N3Y FirstGlance]. <br>
+<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 [http://proteopedia.org/fgij/fg.htm?mol=2N3Y FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MH0:MESOHEME'>MH0</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MH0:MESOHEME'>MH0</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PA:4-(CARBOXYMETHYL)-L-PHENYLALANINE'>1PA</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=2n3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n3y OCA], [http://pdbe.org/2n3y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n3y RCSB], [http://www.ebi.ac.uk/pdbsum/2n3y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n3y ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2n3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n3y OCA], [http://pdbe.org/2n3y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n3y RCSB], [http://www.ebi.ac.uk/pdbsum/2n3y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n3y ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Conte, R Del]]
 [[Category: Diaz-Moreno, I]]

2n3y

From Proteopedia

Revision as of 07:56, 4 November 2020

NMR structure of the Y48pCMF variant of human cytochrome c in its reduced state

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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