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Solid State Nucl Magn Reson. 2017 Nov;88:1-14. doi: 10.1016/j.ssnmr.2017.10.001. Epub 2017 Oct 4.

Insights into protein misfolding and aggregation enabled by solid-state NMR spectroscopy.

Author information

1
Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA. Electronic address: vanderwel@pitt.edu.

Abstract

The aggregation of proteins and peptides into a variety of insoluble, and often non-native, aggregated states plays a central role in many devastating diseases. Analogous processes undermine the efficacy of polypeptide-based biological pharmaceuticals, but are also being leveraged in the design of biologically inspired self-assembling materials. This Trends article surveys the essential contributions made by recent solid-state NMR (ssNMR) studies to our understanding of the structural features of polypeptide aggregates, and how such findings are informing our thinking about the molecular mechanisms of misfolding and aggregation. A central focus is on disease-related amyloid fibrils and oligomers involved in neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's disease. SSNMR-enabled structural and dynamics-based findings are surveyed, along with a number of resulting emerging themes that appear common to different amyloidogenic proteins, such as their compact alternating short-β-strand/β-arc amyloid core architecture. Concepts, methods, future prospects and challenges are discussed.

KEYWORDS:

Amyloid; Magic-angle spinning; Neurodegenerative disease; Prions; Protein dynamics; Protein misfolding; Protein structure; Structural biology

PMID:
29035839
PMCID:
PMC5705391
[Available on 2018-11-01]
DOI:
10.1016/j.ssnmr.2017.10.001

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