Unfolding four-helix bundles

Abstract

A geometrical model has been developed to describe the early stages of unfolding of cytochromes c′ and c-b₅₆₂ . Calculations are based on a step-wise extension of the polypeptide chain subject to the constraint that the spatial relationship among the residues of each triplet is fixed by the native-state crystallographic data. The response of each protein to these structural perturbations allows the evolution of each of the four helices in these two proteins to be differentiated. It is found that the two external helices in c′ unfold before its two internal helices, whereas exactly the opposite behaviour is demonstrated by c-b₅₆₂ . Each of these cytochromes has an extended, internal, non-helical (‘turning’) region that initially lags behind the most labile helix but then, at a certain stage (identified for each cytochrome), unravels before any of the four helices present in the native structure. It is believed that these predictions will be useful in guiding future experimental studies on the unfolding of these two cytochromes.

Keywords:

• cytochrome four-helix bundles
• proteins
• denaturation
• steric constrains