Cytochrome unfolding pathways from computational analysis of crystal structures

Area of Science:

• Biophysics
• Computational Biology
• Protein Folding

Background:

• Understanding protein unfolding is crucial for comprehending protein function and dysfunction.
• Cytochromes are essential proteins involved in electron transport, with complex folding patterns.
• The role of geometrical factors in the initial stages of protein unfolding remains an active area of research.

Purpose of the Study:

• To develop and apply a computational model for studying early unfolding stages in three specific cytochromes.
• To quantify the influence of geometrical factors on protein unfolding dynamics.
• To compare unfolding patterns among cytochrome c', cytochrome c-b562, and cytochrome c.

Main Methods:

• Developed a model to quantify protein unfolding using spatial extension (λ̂i) and angular extension (〈βn〉) of n-residue segments.
• Analyzed unfolding signatures of helical and non-helical regions separately and in tandem.
• Generated graphical portraits for comparative analysis of cytochromes at various unfolding stages relative to native structures.

Main Results:

• Identified similarities and differences in unfolding pathways among the three studied cytochromes.
• Illustrated domain stability variations by analyzing specific segments at different unfolding stages.
• Made specific predictions regarding the unfolding of internal and terminal helices in cytochrome c' and cytochrome c-b562.

Conclusions:

• Geometrical factors significantly influence the early stages of cytochrome unfolding.
• The model provides insights into domain stability and predicts unfolding behavior of specific helices.
• Findings align with experimental evidence regarding the persistent hydrophobic core in cytochrome c.