Electron transfer interactome of cytochrome C

Area of Science:

• Biochemistry
• Computational Biology
• Structural Biology

Background:

• Biological electron transfer (ET) is crucial for cellular processes like photosynthesis and respiration.
• Understanding ET complexes is vital for cellular signaling and metabolism, but their transient nature and binding promiscuity pose challenges.
• Eukaryotic cytochrome c (Cc) is a key electron carrier in mitochondrial respiration and other redox systems.

Purpose of the Study:

• To computationally predict electron transfer (ET) properties of cytochrome c (Cc) protein complexes.
• To map functional epitopes and assess ET rates based solely on protein steric properties.
• To investigate the influence of binding stoichiometry and protein dynamics on intermolecular ET.

Main Methods:

• Utilized a computational approach based on steric properties of individual proteins.
• Performed extensive conformational sampling to identify ET-competent binding geometries.
• Analyzed functional epitopes, ET rates, binding stoichiometries, and domain mobility effects.

Main Results:

• Identified that most ET-competent binding geometries are in electrostatically favorable regions.
• Demonstrated that ET can occur from multiple protein-protein orientations.
• Found protein dynamics, rather than electron tunneling, to be the rate-limiting step in intermolecular ET.

Conclusions:

• The size of the functional epitope correlates with protein dynamics in Cc complexes.
• Protein mobility can be diagnosed using functional epitope size.
• This computational method provides insights into the dynamic nature of electron transfer complexes.