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Compensatory Adaptations of Structural Dynamics in an Intrinsically Disordered Protein Complex
Author(s) -
Kurzbach Dennis,
Schwarz Thomas C.,
Platzer Gerald,
Höfler Simone,
Hinderberger Dariush,
Konrat Robert
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201308389
Subject(s) - intrinsically disordered proteins , context (archaeology) , biophysics , chemistry , ligand (biochemistry) , plasma protein binding , binding site , electron paramagnetic resonance , osteopontin , crystallography , protein structure , chemical physics , biochemistry , physics , biology , nuclear magnetic resonance , paleontology , receptor , immunology
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.