Phi-Value and NMR Structural Analysis of a Coupled Native-State Prolyl Isomerization and Conformational Protein Folding Process.

ABSTRACT: Prolyl cis/trans isomerization is a rate-limiting step in protein folding, often coupling directly to the acquisition of native structure. Here, we investigated the interplay between folding and prolyl isomerization in the N2 domain of the gene-3-protein from filamentous phage fd, which adopts a native-state cis/trans equilibrium at Pro161. Using mutational and Φ-value analysis, we identified a discrete folding nucleus encompassing the β-strands surrounding Pro161. These native-like interactions form early in the folding pathway and provide the energy to shift the cis/trans equilibrium toward the cis form. Variations distant from the Pro161-loop have minimal impact on the cis/trans ratio, underscoring the spatial specificity and local

SUBMITTER: Weininger U 

PROVIDER: S-EPMC11852654 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature