title: A frustrated binding interface for intrinsically disordered proteins.
abstract: 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.
authors.affiliation: From the Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75123 Uppsala, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Jemth
authors.forename: Xin
authors.initials: X
authors.lastname: Mu
authors.forename: Åke
authors.initials: Å
authors.lastname: Engström
authors.forename: Jakob
authors.initials: J
authors.lastname: Dogan
mesh_terms: D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D056921:Nuclear Receptor Coactivator 3 / Q000737:chemistry* / Q000235:genetics; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D011994:Recombinant Proteins; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3
keywords: Intrinsically Disordered Proteins; Kinetics; Protein Domains; Protein Engineering; Protein-Protein Interactions