Mechanism of electron transfers mediated by cytochromes c and b5 in mitochondria and endoplasmic reticulum: classical and murburn perspectives
| Autor: | Kelath Murali Manoj, Daniel Andrew Gideon, Karthik S Sudarsha, Jesu Castin E, Vijay Nirusimhan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Journal of Biomolecular Structure and Dynamics. 40:9235-9252 |
| ISSN: | 1538-0254 0739-1102 |
| Popis: | We explore the mechanism of electron transfers mediated by cytochrome c, a soluble protein involved in mitochondrial oxidative phosphorylation and cytochrome b5, a microsomal membrane protein acting as a redox aide in xenobiotic metabolism. We found minimal conservation in the sequence and surface amino acid residues of cytochrome c/b5 proteins among divergent species. Therefore, we question the evolutionary logic for electron transfer (ET) occurring through affinity binding via recognition of specific surface residues/topography. Also, analysis of putative protein-protein interactions in the crystal structures of these proteins and their redox partners did not point to any specific interaction logic. A comparison of the kinetic and thermodynamic constants of wildtype vs. mutants did not provide strong evidence to support the binding-based ET paradigm, but indicated support for diffusible reactive species (DRS)-mediated process. Topographically divergent cytochromes from one species have been substituted for reaction with proteins from other species, implying the involvement of non-specific interactions. We provide a viable alternative (murburn concept) to classical protein-protein binding-based long range ET mechanism. To account for the promiscuity of interactions and solvent-accessible hemes, we propose that the two proteins act as non- specific redox capacitors, mediating one-electron redox equilibriums involving DRS and unbound ions. Communicated by Ramaswamy H. Sarma |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|