Dissecting the Structural Features of Folding Asymmetry and Transient Misfolding in a Multidomain PDZ Scaffold.

ABSTRACT: Understanding how multidomain proteins fold, avoid misfolding, and maintain functional regulation represents a critical problem in structural biology, with broad relevance for biotechnology. In this study, the tandem PDZ1-PDZ2 domains of the scaffold protein X11, a system of particular interest due to its previously reported asymmetric folding and unfolding behavior as well as its propensity to form transient misfolded intermediates, are investigated. Through extensive mutational work and in-depth kinetic folding analysis, the folding behavior of this multidomain construct is dissected, and a comparative analysis with its isolated PDZ domains is also performed. The results reveal that folding and unfolding proceed through distinct pathways with PDZ2 folding rapidly and independently, while

SUBMITTER: Pennacchietti V 

PROVIDER: S-EPMC12798790 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature