Mapping Long-Range Interactions in α-Synuclein using Spin-Label NMR and Ensemble Molecular Dynamics Simulations

2004/12/21 by Matthew M. Dedmon, Kresten Lindorff‐Larsen, John Christodoulou +2 · 1 voice · 4 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Parkinson's Disease Mechanisms and Treatments #Electron Spin Resonance Studies #Advanced MRI Techniques and Applications

paper · doi:10.1021/ja044834j

Abstract

The intrinsically disordered protein alpha-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD). We show here that the native state of alpha-synuclein consists of a broad distribution of conformers with an ensemble-averaged hydrodynamic radius significantly smaller than that expected for a random coil structure. This partial condensation is driven by interactions between the highly charged C-terminus and a large hydrophobic central region of the protein sequence. We suggest that this structure could inhibit the formation of alpha-synuclein aggregates, which are thought to be the cytotoxic species responsible for neurodegeneration in PD.

Cited by

• Principles of protein structural ensemble determination
• Protein Misfolding, Functional Amyloid, and Human Disease
• Accurate model of liquid–liquid phase behavior of intrinsically disordered proteins from optimization of single-chain properties
• Advancing Protein Ensemble Predictions Across the Order–Disorder Continuum

Discussions

• It’s been 20 years today since my first paper on intrinsically disordered proteins Mapping Long-Range Interactions in α-Synuclein using Spin-Label NMR and Ensemble Molecular Dynamics Simulations doi. [bsky, 76 points, 3 comments]

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