Long-Range Correlated Dynamics in Intrinsically Disordered Proteins

• Published in: Journal of the American Chemical Society Vol. 136; no. 46; pp. 16201 - 16209
• Main Authors: Parigi, Giacomo, Rezaei-Ghaleh, Nasrollah, Giachetti, Andrea, Becker, Stefan, Fernandez, Claudio, Blackledge, Martin, Griesinger, Christian, Zweckstetter, Markus, Luchinat, Claudio
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19.11.2014
• Subjects: alpha-Synuclein - chemistry; alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Animals; Biochemistry, Molecular Biology; Chemical Phenomena; Intrinsically Disordered Proteins - chemistry; Intrinsically Disordered Proteins - genetics; Intrinsically Disordered Proteins - metabolism; Life Sciences; Models, Molecular; Mutation; Protein Conformation; Protons; Structural Biology; Temperature; Water - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja506820r

Intrinsically disordered proteins (IDPs) are involved in a wide variety of physiological and pathological processes and are best described by ensembles of rapidly interconverting conformers. Using fast field cycling relaxation measurements we here show that the IDP α-synuclein as well as a variety of other IDPs undergoes slow reorientations at time scales comparable to folded proteins. The slow motions are not perturbed by mutations in α-synuclein, which are related to genetic forms of Parkinson’s disease, and do not depend on secondary and tertiary structural propensities. Ensemble-based hydrodynamic calculations suggest that the time scale of the underlying correlated motion is largely determined by hydrodynamic coupling between locally rigid segments. Our study indicates that long-range correlated dynamics are an intrinsic property of IDPs and offers a general physical mechanism of correlated motions in highly flexible biomolecular systems.