Title |
Side-Chain Interactions Form Late and Cooperatively in the Binding Reaction between Disordered Peptides and PDZ Domains
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Published in |
Journal of the American Chemical Society, December 2011
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DOI | 10.1021/ja209341w |
Pubmed ID | |
Authors |
S. Raza Haq, Celestine N. Chi, Anders Bach, Jakob Dogan, Åke Engström, Greta Hultqvist, O. Andreas Karlsson, Patrik Lundström, Linda C. Montemiglio, Kristian Strømgaard, Stefano Gianni, Per Jemth |
Abstract |
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). |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 2 | 3% |
Italy | 1 | 2% |
Korea, Republic of | 1 | 2% |
Canada | 1 | 2% |
United Kingdom | 1 | 2% |
Unknown | 59 | 91% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 21 | 32% |
Researcher | 10 | 15% |
Student > Master | 6 | 9% |
Student > Bachelor | 4 | 6% |
Professor | 4 | 6% |
Other | 10 | 15% |
Unknown | 10 | 15% |
Readers by discipline | Count | As % |
---|---|---|
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Agricultural and Biological Sciences | 17 | 26% |
Biochemistry, Genetics and Molecular Biology | 15 | 23% |
Unspecified | 1 | 2% |
Arts and Humanities | 1 | 2% |
Other | 4 | 6% |
Unknown | 10 | 15% |