Open AccessStructural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance
Author(s) -
Adam N. Smith,
Katharina Märker,
Talia Piretra,
Jennifer C. Boatz,
Irina Matlahov,
Ravindra Kodali,
Sabine Hediger,
Patrick C.A. van der Wel,
Gaël De Paëpe
Publication year - 2018
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.8b09002
Subject(s) - chemistry , natural abundance , solid state nuclear magnetic resonance , isotopic labeling , huntingtin , isotope , abundance (ecology) , mutant , mass spectrometry , nuclear magnetic resonance , biochemistry , chromatography , physics , organic chemistry , fishery , biology , gene , quantum mechanics
A pathological hallmark of Huntington's disease (HD) is the formation of neuronal protein deposits containing mutant huntingtin fragments with expanded polyglutamine (polyQ) domains. Prior studies have shown the strengths of solid-state NMR (ssNMR) to probe the atomic structure of such aggregates, but have required in vitro isotopic labeling. Herein, we present an approach for the structural fingerprinting of fibrils through ssNMR at natural isotopic abundance (NA). These methods will enable the spectroscopic fingerprinting of unlabeled (e.g., ex vivo) protein aggregates and the extraction of valuable new long-range 13 C- 13 C distance constraints.
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