Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 57, Issue 46, Pages 15262-15266Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201808172
Keywords
intrinsically disordered proteins; NMR spectroscopy; protein dynamics
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Funding
- European Research Council [787679 - LLPS-NMR]
- Fondazione Cassa di Risparmio di Firenze, MIUR [PRIN 2012SK7ASN]
- European Commission [634821, 653706]
- COST Action [CA15209]
- EU ESFRI Instruct Core Centre CERM
- Swiss National Science Foundation
- Deutsche Forschungsgemeinschaft [RE 3655/2-1]
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Intrinsically disordered proteins (IDPs) experience a diverse spectrum of motions that are difficult to characterize with a single experimental technique. Herein we combine high-and low-field nuclear spin relaxation, nanosecond fluorescence correlation spectroscopy (nsFCS), and long molecular dynamics simulations of alpha-synuclein, an IDP involved in Parkinson disease, to obtain a comprehensive picture of its conformational dynamics. The combined analysis shows that fast motions below 2 ns caused by local dihedral angle fluctuations and conformational sampling within and between Ramachandran substates decorrelate most of the backbone N-H orientational memory. However, slow motions with correlation times of up to ca. 13 ns from segmental dynamics are present throughout the alpha-synuclein chain, in particular in its C-terminal domain, and global chain reconfiguration occurs on a timescale of ca. 60 ns. Our study demonstrates a powerful strategy to determine residue-specific protein dynamics in IDPs at different time and length scales.
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