Oxidative Folding Pathway of Onconase, a Ribonuclease Homologue: Insight into Oxidative Folding Mechanisms from a Study of Two Homologues

摘要

The oxidative folding pathways of two four-disulfide proteins of the ribonuclease family, ONCnand RNase A, which have similar three-dimensional folds but only 30% sequence homology, are compared.nIn this study, a mechanism for the oxidative folding pathway of ONC is proposed. In particular, thenkinetic roles and thermodynamic characteristics of key intermediates along the oxidative folding pathway,nspecifically, the structured intermediates, I1, I2, and I3, previously identified as des-[19-68,30-75], des-n[30-75], and des-[19-68], respectively, are discussed. In addition, the effects of temperature on thenoxidative folding pathway have been examined. Differences in the folding mechanism between ONC andnRNase A are attributed to the differences in their amino acid sequences and related inter-residue interactions,nincluding differences in hydrophobic interactions. Compared to RNase A, ONC utilizes more efficientninteractions along the oxidative folding pathway to adopt its native fold more rapidly.