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Updated: Jul 10, 2026

Millisecond Hydrogen/Deuterium-Exchange Mass Spectrometry for the Study of Alpha-Synuclein Structural Dynamics Under Physiological Conditions
Published on: June 23, 2022
Solid-state NMR spectroscopy reveals that water is nonessential to the core structure of alpha-synuclein fibrils
Kathryn D Kloepper1, Kevin L Hartman, Daniel T Ladror
1Department of Chemistry, and Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
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 alpha-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.
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