title: NMR Spectroscopic Studies of the Conformational Ensembles of Intrinsically Disordered Proteins.
abstract: Intrinsically disordered proteins (IDPs) are characterized by substantial conformational flexibility and thus not amenable to conventional structural biology techniques. Given their inherent structural flexibility NMR spectroscopy offers unique opportunities for structural and dynamic studies of IDPs. The past two decades have witnessed significant development of NMR spectroscopy that couples advances in spin physics and chemistry with a broad range of applications. This chapter will summarize key advances in NMR methodology. Despite the availability of efficient (multi-dimensional) NMR experiments for signal assignment of IDPs it is discussed that NMR of larger and more complex IDPs demands spectral simplification strategies capitalizing on specific isotope-labeling strategies. Prototypical applications of isotope labeling-strategies are described. Since IDP-ligand association and dissociation processes frequently occur on time scales that are amenable to NMR spectroscopy we describe in detail the application of CPMG relaxation dispersion techniques to studies of IDP protein binding. Finally, we demonstrate that the complementary usage of NMR and EPR data provide a more comprehensive picture about the conformational states of IDPs and can be employed to analyze the conformational ensembles of IDPs.
authors.affiliation: Department of Computational and Structural Biology, Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 5, 1030, Vienna, Austria.
authors.forename: Dennis
authors.initials: D
authors.lastname: Kurzbach
authors.affiliation: Department of Computational and Structural Biology, Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 5, 1030, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Kontaxis
authors.affiliation: Department of Computational and Structural Biology, Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 5, 1030, Vienna, Austria.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Coudevylle
authors.affiliation: Department of Computational and Structural Biology, Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 5, 1030, Vienna, Austria. robert.konrat@univie.ac.at.
authors.forename: Robert
authors.initials: R
authors.lastname: Konrat
mesh_terms: D004578:Electron Spin Resonance Spectroscopy; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation
chemical_list: D064267:Intrinsically Disordered Proteins
keywords: Biomolecular NMR; EPR spectroscopy; Intrinsically disordered proteins; NMR spin relaxation; Paramagnetic relaxation; Protein meta-structure