Side-chain interactions form late and cooperatively in the binding reaction between disordered peptides and PDZ domains

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Side-chain interactions form late and cooperatively in the binding reaction between disordered peptides and PDZ domains. / Haq, S Raza; Chi, Celestine N; Bach, Anders; Dogan, Jakob; Engström, Åke; Hultqvist, Greta; Karlsson, O. Andreas; Lundström, Patrik; Montemiglio, Linda Celeste; Strømgaard, Kristian; Gianni, Stefano; Jemth, Per.

In: Journal of the American Chemical Society, Vol. 134, No. 1, 01.2012, p. 599-605.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Haq, SR, Chi, CN, Bach, A, Dogan, J, Engström, Å, Hultqvist, G, Karlsson, OA, Lundström, P, Montemiglio, LC, Strømgaard, K, Gianni, S & Jemth, P 2012, 'Side-chain interactions form late and cooperatively in the binding reaction between disordered peptides and PDZ domains', Journal of the American Chemical Society, vol. 134, no. 1, pp. 599-605. https://doi.org/10.1021/ja209341w

APA

Haq, S. R., Chi, C. N., Bach, A., Dogan, J., Engström, Å., Hultqvist, G., ... Jemth, P. (2012). Side-chain interactions form late and cooperatively in the binding reaction between disordered peptides and PDZ domains. Journal of the American Chemical Society, 134(1), 599-605. https://doi.org/10.1021/ja209341w

Vancouver

Haq SR, Chi CN, Bach A, Dogan J, Engström Å, Hultqvist G et al. Side-chain interactions form late and cooperatively in the binding reaction between disordered peptides and PDZ domains. Journal of the American Chemical Society. 2012 Jan;134(1):599-605. https://doi.org/10.1021/ja209341w

Author

Haq, S Raza ; Chi, Celestine N ; Bach, Anders ; Dogan, Jakob ; Engström, Åke ; Hultqvist, Greta ; Karlsson, O. Andreas ; Lundström, Patrik ; Montemiglio, Linda Celeste ; Strømgaard, Kristian ; Gianni, Stefano ; Jemth, Per. / Side-chain interactions form late and cooperatively in the binding reaction between disordered peptides and PDZ domains. In: Journal of the American Chemical Society. 2012 ; Vol. 134, No. 1. pp. 599-605.

Bibtex

@article{1a681a891f8b4925ac1f454b1625b88f,
title = "Side-chain interactions form late and cooperatively in the binding reaction between disordered peptides and PDZ domains",
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. We have here 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, 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 towards their targets are generally governed by their association rate constants. Instead, we observe the opposite for peptide-PDZ interactions, namely that changes in Kd correlate with changes in koff.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Haq, {S Raza} and Chi, {Celestine N} and Anders Bach and Jakob Dogan and {\AA}ke Engstr{\"o}m and Greta Hultqvist and Karlsson, {O. Andreas} and Patrik Lundstr{\"o}m and Montemiglio, {Linda Celeste} and Kristian Str{\o}mgaard and Stefano Gianni and Per Jemth",
year = "2012",
month = "1",
doi = "10.1021/ja209341w",
language = "English",
volume = "134",
pages = "599--605",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "ACS Publications",
number = "1",

}

RIS

TY - JOUR

T1 - Side-chain interactions form late and cooperatively in the binding reaction between disordered peptides and PDZ domains

AU - Haq, S Raza

AU - Chi, Celestine N

AU - Bach, Anders

AU - Dogan, Jakob

AU - Engström, Åke

AU - Hultqvist, Greta

AU - Karlsson, O. Andreas

AU - Lundström, Patrik

AU - Montemiglio, Linda Celeste

AU - Strømgaard, Kristian

AU - Gianni, Stefano

AU - Jemth, Per

PY - 2012/1

Y1 - 2012/1

N2 - 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. We have here 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, 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 towards their targets are generally governed by their association rate constants. Instead, we observe the opposite for peptide-PDZ interactions, namely that changes in Kd correlate with changes in koff.

AB - 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. We have here 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, 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 towards their targets are generally governed by their association rate constants. Instead, we observe the opposite for peptide-PDZ interactions, namely that changes in Kd correlate with changes in koff.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/ja209341w

DO - 10.1021/ja209341w

M3 - Journal article

C2 - 22129097

VL - 134

SP - 599

EP - 605

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 1

ER -

ID: 35412490