1. Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc1 perturbs heme bH redox potential and spin state
- Author
-
Patryk Kuleta, Iwona Ekiert, Artur Osyczka, Marcin Sarewicz, Vivek Sharma, Jonathan Lasham, Robert Ekiert, Materials Physics, Department of Physics, and Institute of Biotechnology
- Subjects
DYNAMICS ,Models, Molecular ,Protein Conformation ,Antimycin A ,BIS-HISTIDINE ,01 natural sciences ,Rhodobacter capsulatus ,chemistry.chemical_compound ,Electron Transport Complex III ,UBIQUINOL-CYTOCHROME-C2 OXIDOREDUCTASE ,ELECTRON-TRANSFER ,BC(1) ,Heme ,0303 health sciences ,Multidisciplinary ,biology ,Cytochrome bc1 ,Chemistry ,Cytochrome b ,Biological Sciences ,electron transfer ,Mitochondria ,COMPLEX-III ,INTERFACE ,electron paramagnetic resonance ,Oxidation-Reduction ,Hemeprotein ,010402 general chemistry ,Redox ,114 Physical sciences ,Cofactor ,RHODOBACTER-CAPSULATUS ,03 medical and health sciences ,Electron transfer ,mitochondrial dysfunction ,Q(O) SITE ,density functional theory ,030304 developmental biology ,Spectrum Analysis ,Electron Spin Resonance Spectroscopy ,Hydrogen Bonding ,CORRELATION-ENERGY ,molecular dynamics simulations ,Cytochrome b Group ,0104 chemical sciences ,Biophysics and Computational Biology ,Coenzyme Q – cytochrome c reductase ,Mutation ,biology.protein ,Biophysics - Abstract
Significance To perform their specific electron-transfer relay functions, hemes commonly adopt low spin states with fine-tuned redox potentials. Understanding molecular elements controlling these properties is crucial for the description of natural proteins and engineering redox-active systems. We describe unusual effects of mitochondrial disease-related mutation in cytochrome bc1, based on which we identify a dual role of hydrogen bonding to the propionate group of heme bH. We observe that stabilization of the hydrogen bond in mutant enhances the redox potential but destabilizes the low spin state of oxidized heme. This demonstrates a critical role of the hydrogen bonding, and heme-protein interactions in general, to secure a suitable redox potential and spin state, a notion that might be universal for other heme proteins., Hemes are common elements of biological redox cofactor chains involved in rapid electron transfer. While the redox properties of hemes and the stability of the spin state are recognized as key determinants of their function, understanding the molecular basis of control of these properties is challenging. Here, benefiting from the effects of one mitochondrial disease–related point mutation in cytochrome b, we identify a dual role of hydrogen bonding (H-bond) to the propionate group of heme bH of cytochrome bc1, a common component of energy-conserving systems. We found that replacing conserved glycine with serine in the vicinity of heme bH caused stabilization of this bond, which not only increased the redox potential of the heme but also induced structural and energetic changes in interactions between Fe ion and axial histidine ligands. The latter led to a reversible spin conversion of the oxidized Fe from 1/2 to 5/2, an effect that potentially reduces the electron transfer rate between the heme and its redox partners. We thus propose that H-bond to the propionate group and heme-protein packing contribute to the fine-tuning of the redox potential of heme and maintaining its proper spin state. A subtle balance is needed between these two contributions: While increasing the H-bond stability raises the heme potential, the extent of increase must be limited to maintain the low spin and diamagnetic form of heme. This principle might apply to other native heme proteins and can be exploited in engineering of artificial heme-containing protein maquettes.
- Published
- 2021