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

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

doi:10.1021/jacs.8b09002

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

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

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

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.

Original language	English
Pages (from-to)	14576-14580
Number of pages	5
Journal	Journal of the American Chemical Society
Volume	140
Issue number	44
DOIs	https://doi.org/10.1021/jacs.8b09002
State	Published - 7 Nov 2018
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2018 American Chemical Society.

Funding

The authors thank Drs. Daniel Lee and Diego Gauto for helpful discussions, and Dr. James Conway for use of the EM facility. This work was funded by European Union Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Action-795423-BOLD-NMR (A.N.S.), European Research Council grant ERC-CoG-2015 No. 682895 (G.D.P), and NIH grants R01 GM112678 (P.v.d.W.) and T32 GM088119 (J.C.B.).

Funders	Funder number
National Institutes of Health	R01 GM112678
National Institute of General Medical Sciences	T32GM088119
European Commission	ERC-CoG-2015, 682895

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Smith, A. N., Märker, K., Piretra, T., Boatz, J. C., Matlahov, I., Kodali, R., Hediger, S., Van Der Wel, P. C. A., & De Paëpe, G. (2018). Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance. Journal of the American Chemical Society, 140(44), 14576-14580. https://doi.org/10.1021/jacs.8b09002

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Smith, AN, Märker, K, Piretra, T, Boatz, JC, Matlahov, I, Kodali, R, Hediger, S, Van Der Wel, PCA & De Paëpe, G 2018, 'Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance', Journal of the American Chemical Society, vol. 140, no. 44, pp. 14576-14580. https://doi.org/10.1021/jacs.8b09002

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

Abstract

Bibliographical note

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