Title: Folding and misfolding in a naturally occurring circularly permuted PDZ domain
Authors: Ivarsson, Ylva
Travaglini-Allocatelli, Carlo
Brunori, Maurizio
Gianni, Stefano # ×
Issue Date: Apr-2008
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of biological chemistry vol:283 issue:14 pages:8954-8960
Abstract: One of the most extreme and fascinating examples of naturally occurring mutagenesis is represented by circular permutation. Circular permutations involve the linking of two chain ends and cleavage at another site. Here we report the first description of the folding mechanism of a naturally occurring circularly permuted protein, a PDZ domain from the green alga Scenedesmus obliquus. Data reveal that the folding of the permuted protein is characterized by the presence of a low energy off-pathway kinetic trap. This finding contrasts with what was previously observed for canonical PDZ domains that, although displaying a similar primary structure when structurally re-aligned, fold via an on-pathway productive intermediate. Although circular permutation of PDZ domains may be necessary for a correct orientation of their functional sites in multidomain protein scaffolds, such structural rearrangement may compromise their folding pathway. This study provides a straightforward example of the divergent demands of folding and function.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Laboratory for Signal Integration in Cell Fate Decision
× corresponding author
# (joint) last author

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