Title: Engineered Symmetric Connectivity of Secondary Structure Elements Highlights Malleability of Protein Folding Pathways
Authors: Ivarsson, Ylva
Travaglini-Allocatelli, Carlo
Brunori, Maurizio
Gianni, Stefano # ×
Issue Date: 26-Aug-2009
Publisher: American Chemical Society
Series Title: Journal of the American Chemical Society vol:131 issue:33 pages:11727-11733
Abstract: To understand the role of sequence connectivity in protein folding pathways, we explored by Phi-value analysis the folding pathway of an engineered circularly permuted PDZ domain. This variant has the same sequence connectivity as naturally occurring circularly permuted PDZ domains and displays a symmetrical distribution of secondary structure elements (i.e., beta beta alpha beta beta alpha beta beta) while maintaining the same tertiary interactions of the well-characterized second PDZ domain from PTP-BL (PDZ2). Reliable Phi values were obtained for both a low-energy intermediate and the late rate-limiting transition state, allowing a description of both early and late events in folding. A comparison with Phi values obtained for wild-type PDZ2 reveals that while the structure of the late transition state is robust and unaffected by circular permutation, the folding intermediate is stabilized by a different nucleus involving residues located at the new N- and C-termini. The results suggest that folding is driven by competing nuclei whose stabilities may be selectively tuned by circular permutation.
ISSN: 0002-7863
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Signal Integration in Cell Fate Decision
× corresponding author
# (joint) last author

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