Molecular Interactions between Neuroglobin and Cytochrome c: Possible Mechanisms of Antiapoptotic Defense in Neuronal Cells

Semenova, Marina A.; Chertkova, Rita V.; Kirpichnikov, Mikhaǐl P.; Долгих, Д. А.

doi:10.3390/biom13081233

Cited by 1 publication

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“…Notably, some peripheral Lys residues, for instance, at positions 73 and 79, are sometimes also referred to as key UBS residues. Of interest, the role of Lys residues from this series is also decisive in the interaction of CytC with a wide variety of other partners of protein and non-protein nature-cytochrome c -peroxidase [ 32 ], cytochrome b5 [ 33 ], Apaf-1 [ 34 ], CL [ 35 ], histone chaperones [ 36 ], neuroglobin [ 37 ] and others [ 7 ], which confirms the versatility of this CytC site.…”

Section: Resultsmentioning

confidence: 86%

Mutant Cytochrome C as a Potential Detector of Superoxide Generation: Effect of Mutations on the Function and Properties

Chertkova,

Oleynikov,

Pakhomov

et al. 2023

Cells

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Cytochrome c (CytC) is a single-electron carrier between complex bc1 and cytochrome c-oxidase (CcO) in the electron transport chain (ETC). It is also known as a good radical scavenger but its participation in electron flow through the ETC makes it impossible to use CytC as a radical sensor. To solve this problem, a series of mutants were constructed with substitutions of Lys residues in the universal binding site (UBS) which interact electrostatically with negatively charged Asp and Glu residues at the binding sites of CytC partners, bc1 complex and CcO. The aim of this study was to select a mutant that had lost its function as an electron carrier in the ETC, retaining the structure and ability to quench radicals. It was shown that a mutant CytC with substitutions of five (8Mut) and four (5Mut) Lys residues in the UBS was almost inactive toward CcO. However, all mutant proteins kept their antioxidant activity sufficiently with respect to the superoxide radical. Mutations shifted the dipole moment of the CytC molecule due to seriously changed electrostatics on the surface of the protein. In addition, a decrease in the redox potential of the protein as revealed by the redox titrations of 8Mut was detected. Nevertheless, the CD spectrum and dynamic light scattering suggested no significant changes in the secondary structure or aggregation of the molecules of CytC 8Mut. Thus, a variant 8Mut with multiple mutations in the UBS which lost its ability to electron transfer and saved most of its physico-chemical properties can be effectively used as a detector of superoxide generation both in mitochondria and in other systems.

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