A Frustrated Binding Interface for Intrinsically Disordered Proteins
2014 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 289, no 9, 5528-5533 p.Article in journal (Refereed) Published
Background: Protein-protein interactions often involve intrinsically disordered protein domains. Results: The binding interface between two disordered protein domains is suboptimal, or frustrated, with regard to the energetics. Conclusion: The frustration likely results from the promiscuous binding behavior of these disordered domains. Significance: Suboptimal binding interfaces may be common among intrinsically disordered proteins with multiple binding partners. Intrinsically disordered proteins are very common in the eukaryotic proteome, and many of them are associated with diseases. Disordered proteins usually undergo a coupled binding and folding reaction and often interact with many different binding partners. Using double mutant cycles, we mapped the energy landscape of the binding interface for two interacting disordered domains and found it to be largely suboptimal in terms of interaction free energies, despite relatively high affinity. These data depict a frustrated energy landscape for interactions involving intrinsically disordered proteins, which is likely a result of their functional promiscuity.
Place, publisher, year, edition, pages
2014. Vol. 289, no 9, 5528-5533 p.
Intrinsically Disordered Proteins, Kinetics, Protein Domains, Protein Engineering, Protein-Protein Interactions
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-227573DOI: 10.1074/jbc.M113.537068ISI: 000332015500017OAI: oai:DiVA.org:uu-227573DiVA: diva2:730858