title: Compensatory adaptations of structural dynamics in an intrinsically disordered protein complex.
abstract: Intrinsically disordered proteins (IDPs) play crucial roles in protein interaction networks and in this context frequently constitute important hubs and interfaces. Here we show by a combination of NMR and EPR spectroscopy that the binding of the cytokine osteopontin (OPN) to its natural ligand, heparin, is accompanied by thermodynamically compensating structural adaptations. The core segment of OPN expands upon binding. This "unfolding-upon-binding" is governed primarily through electrostatic interactions between heparin and charged patches along the protein backbone and compensates for entropic penalties due to heparin-OPN binding. It is shown how structural unfolding compensates for entropic losses through ligand binding in IDPs and elucidates the interplay between structure and thermodynamics of rapid substrate-binding and -release events in IDP interaction networks.
authors.affiliation: Department of Structural and Computational Biology, Max F. Perutz Laboratories, Vienna Biocenter Campus 5, 1030 Vienna (Austria).
authors.forename: Dennis
authors.initials: D
authors.lastname: Kurzbach
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Schwarz
authors.forename: Gerald
authors.initials: G
authors.lastname: Platzer
authors.forename: Simone
authors.initials: S
authors.lastname: Höfler
authors.forename: Dariush
authors.initials: D
authors.lastname: Hinderberger
authors.forename: Robert
authors.initials: R
authors.lastname: Konrat
mesh_terms: D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D060066:Protein Interaction Maps / Q000502:physiology*; D013816:Thermodynamics
chemical_list: D064267:Intrinsically Disordered Proteins
keywords: NMR spectroscopy; compensatory entropy; intrinsically disordered proteins; osteopontin; protein complexes