Structural and functional characterization of phosphomimetic mutants of cytochrome c at threonine 28 and serine 47

Biochimica Et Biophysica Acta
Alejandra Guerra-CastellanoAntonio Díaz-Quintana

Abstract

Protein function is frequently modulated by post-translational modifications of specific residues. Cytochrome c, in particular, is phosphorylated in vivo at threonine 28 and serine 47. However, the effect of such modifications on the physiological functions of cytochrome c - namely, the transfer of electrons in the respiratory electron transport chain and the triggering of programmed cell death - is still unknown. Here we replace each of these two residues by aspartate, in order to mimic phosphorylation, and report the structural and functional changes in the resulting cytochrome c variants. We find that the T28D mutant causes a 30-mV decrease on the midpoint redox potential and lowers the affinity for the distal site of Arabidopsis thaliana cytochrome c1 in complex III. Both the T28D and S47D variants display a higher efficiency as electron donors for the cytochrome c oxidase activity of complex IV. In both protein mutants, the peroxidase activity is significantly higher, which is related to the ability of cytochrome c to leave the mitochondria and reach the cytoplasm. We also find that both mutations at serine 47 (S47D and S47A) impair the ability of cytoplasmic cytochrome c to activate the caspases cascade, which is essentia...Continue Reading

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Citations

Sep 18, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hasini A KalpageMaik Hüttemann
Mar 8, 2018·Cell Death & Disease·Carlos A Elena-RealIrene Díaz-Moreno
Nov 22, 2018·BMC Cell Biology·Tylor R LewisJoseph C Besharse
Oct 31, 2019·FEBS Letters·Katiuska González-ArzolaMiguel Á De la Rosa
Oct 2, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hasini A KalpageMaik Hüttemann
May 8, 2020·Oxidative Medicine and Cellular Longevity·Antonio Díaz-QuintanaIrene Díaz-Moreno
Mar 30, 2017·Proceedings of the National Academy of Sciences of the United States of America·Blas Moreno-BeltránIrene Díaz-Moreno
Jul 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Alejandra Guerra-CastellanoIrene Díaz-Moreno
Jul 31, 2020·Computational and Structural Biotechnology Journal·Gonzalo Pérez-MejíasIrene Díaz-Moreno
Nov 15, 2020·International Journal of Molecular Sciences·Alejandra Guerra-CastellanoIrene Díaz-Moreno
Dec 24, 2020·The Plant Journal : for Cell and Molecular Biology·Carlos A Elena-RealIrene Díaz-Moreno
Feb 6, 2020·The International Journal of Biochemistry & Cell Biology·Hasini A KalpageMaik Hüttemann
Jul 28, 2020·Biochimica Et Biophysica Acta. Bioenergetics·Gonzalo Pérez-MejíasIrene Díaz-Moreno
May 4, 2021·FEBS Open Bio·Katiuska González-ArzolaMiguel A De la Rosa
Jul 6, 2021·Archives of Biochemistry and Biophysics·Sasiprapa Samsri, Soraya Pornsuwan
Oct 14, 2017·Chemical Reviews·Damián Alvarez-PaggiDaniel H Murgida

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