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Side-Chain Interactions Form Late and Cooperatively in the Binding Reaction between Disordered Peptides and PDZ Domains
Uppsala University.
Uppsala University.
University of Copenhagen.
Uppsala University.
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2012 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, no 1, 599-605 p.Article in journal (Refereed) Published
Abstract [en]

Intrinsically disordered proteins are very common and mediate numerous protein-protein and protein-DNA interactions. While it is clear that these interactions are instrumental for the life of the mammalian cell, there is a paucity of data regarding their molecular binding mechanisms. Here we have used short peptides as a model system for intrinsically disordered proteins. Linear free energy relationships based on rate and equilibrium constants for the binding of these peptides to ordered target proteins, PDZ domains, demonstrate that native side-chain interactions form mainly after the rate-limiting barrier for binding and in a cooperative fashion. This finding suggests that these disordered peptides first form a weak encounter complex with non-native interactions. The data do not support the recent notion that the affinities of intrinsically disordered proteins toward their targets are generally governed by their association rate constants. Instead, we observed the opposite for peptide-PDZ interactions, namely, that changes in K-d correlate with changes in k(off).

Place, publisher, year, edition, pages
American Chemical Society , 2012. Vol. 134, no 1, 599-605 p.
National Category
Engineering and Technology
URN: urn:nbn:se:liu:diva-76201DOI: 10.1021/ja209341wISI: 000301084200096OAI: diva2:513116
Funding Agencies|Swedish Research Council|2009-56592008-4285|Human Frontiers Science Program||Danish Research Council||Available from: 2012-03-30 Created: 2012-03-30 Last updated: 2012-03-30

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