Solid-State NMR Spectroscopy Reveals That Water Is Nonessential to the Core Structure of α-Synuclein Fibrils
- 1 November 2007
- journal article
- letter
- Published by American Chemical Society (ACS) in The Journal of Physical Chemistry B
- Vol. 111 (47), 13353-13356
- https://doi.org/10.1021/jp077036z
Abstract
Protein aggregation is implicated in the etiology of numerous neurodegenerative diseases. An understanding of aggregation mechanisms is enhanced by atomic-resolution structural information, of which relatively little is currently available. Lewy bodies, the pathological hallmark of Parkinson's disease, contain large quantities of fibrillar α-synuclein (AS). Here we present solid-state NMR spectroscopy studies of dried AS fibrils. The spectra have high resolution and sensitivity, and the site-resolved chemical shifts agree very well with those previously observed for hydrated fibrils. The conserved chemical shifts indicate that bulk water is nonessential to the fibril core structure. Moreover, the sample preparation procedure yields major improvements in spectral sensitivity, without compromising spectral resolution. This advance will greatly assist the atomic-resolution structural analysis of AS fibrils.Keywords
This publication has 24 references indexed in Scilit:
- The new mutation, E46K, of α‐synuclein causes parkinson and Lewy body dementiaAnnals of Neurology, 2003
- Structural Organization of α-Synuclein Fibrils Studied by Site-directed Spin LabelingJournal of Biological Chemistry, 2003
- Chemical shift referencing in MAS solid state NMRJournal of Magnetic Resonance, 2003
- A structural model for Alzheimer's β-amyloid fibrils based on experimental constraints from solid state NMRProceedings of the National Academy of Sciences, 2002
- 3D TEDOR NMR Experiments for the Simultaneous Measurement of Multiple Carbon−Nitrogen Distances in Uniformly13C,15N-Labeled SolidsJournal of the American Chemical Society, 2002
- Supramolecular Structure in Full-Length Alzheimer's β-Amyloid Fibrils: Evidence for a Parallel β-Sheet Organization from Solid-State Nuclear Magnetic ResonanceBiophysical Journal, 2002
- Amyloid fibers are water-filled nanotubesProceedings of the National Academy of Sciences, 2002
- Fibrils Formed in Vitro from α-Synuclein and Two Mutant Forms Linked to Parkinson's Disease are Typical AmyloidBiochemistry, 2000
- Mutation in the α-Synuclein Gene Identified in Families with Parkinson's DiseaseScience, 1997
- NMRPipe: A multidimensional spectral processing system based on UNIX pipesJournal of Biomolecular NMR, 1995