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Engineered symmetric connectivity of secondary structure elements highlights malleability of protein folding pathways
University of Rome, La Sapienza. (Ivarsson)
2009 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 33, 11727-33 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 131, no 33, 11727-33 p.
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-203349DOI: 10.1021/ja900438bPubMedID: 19722594OAI: oai:DiVA.org:uu-203349DiVA: diva2:636250
Available from: 2013-07-09 Created: 2013-07-09 Last updated: 2013-07-12Bibliographically approved

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