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

Adam Smith (1) , Katharina Märker (1) , Talia Piretra (2) , Jennifer Boatz (2) , Irina Matlahov (2) , Ravindra Kodali (3) , Sabine Hediger (1, 4) , Patrick van Der Wel (2) , Gaël de Paëpe (1)

1 RM - Magnetic Resonance
2 University of Pittsburgh School of Medicine
3 Duquesne University [Pittsburgh]
4 CNRS - Centre National de la Recherche Scientifique

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

Domaines: Chimie; Biologie structurale [q-bio.BM]

Adam Smith, Katharina Märker, Talia Piretra, Jennifer Boatz, Irina Matlahov, et al.. Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance. Journal of the American Chemical Society, 2018, 140 (44), pp.14576-14580. ⟨10.1021/jacs.8b09002⟩. ⟨hal-02044496⟩