Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance

J Am Chem Soc. 2018 Nov 7;140(44):14576-14580. doi: 10.1021/jacs.8b09002. Epub 2018 Oct 26.

Abstract

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 13C-13C distance constraints.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon Isotopes
  • Humans
  • Huntingtin Protein / chemistry*
  • Nitrogen Isotopes
  • Nuclear Magnetic Resonance, Biomolecular*
  • Particle Size
  • Protein Aggregates
  • Protein Conformation

Substances

  • Carbon Isotopes
  • HTT protein, human
  • Huntingtin Protein
  • Nitrogen Isotopes
  • Protein Aggregates