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

[Image: see text] 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...

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Autores principales: Smith, Adam N., Märker, Katharina, Piretra, Talia, Boatz, Jennifer C., Matlahov, Irina, Kodali, Ravindra, Hediger, Sabine, van der Wel, Patrick C. A., De Paëpe, Gaël
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287890/
https://www.ncbi.nlm.nih.gov/pubmed/30339373
http://dx.doi.org/10.1021/jacs.8b09002
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author Smith, Adam N.
Märker, Katharina
Piretra, Talia
Boatz, Jennifer C.
Matlahov, Irina
Kodali, Ravindra
Hediger, Sabine
van der Wel, Patrick C. A.
De Paëpe, Gaël
author_facet Smith, Adam N.
Märker, Katharina
Piretra, Talia
Boatz, Jennifer C.
Matlahov, Irina
Kodali, Ravindra
Hediger, Sabine
van der Wel, Patrick C. A.
De Paëpe, Gaël
author_sort Smith, Adam N.
collection PubMed
description [Image: see text] 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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spelling pubmed-62878902018-12-12 Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance Smith, Adam N. Märker, Katharina Piretra, Talia Boatz, Jennifer C. Matlahov, Irina Kodali, Ravindra Hediger, Sabine van der Wel, Patrick C. A. De Paëpe, Gaël J Am Chem Soc [Image: see text] 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. American Chemical Society 2018-10-19 2018-11-07 /pmc/articles/PMC6287890/ /pubmed/30339373 http://dx.doi.org/10.1021/jacs.8b09002 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Smith, Adam N.
Märker, Katharina
Piretra, Talia
Boatz, Jennifer C.
Matlahov, Irina
Kodali, Ravindra
Hediger, Sabine
van der Wel, Patrick C. A.
De Paëpe, Gaël
Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance
title Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance
title_full Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance
title_fullStr Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance
title_full_unstemmed Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance
title_short Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance
title_sort structural fingerprinting of protein aggregates by dynamic nuclear polarization-enhanced solid-state nmr at natural isotopic abundance
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287890/
https://www.ncbi.nlm.nih.gov/pubmed/30339373
http://dx.doi.org/10.1021/jacs.8b09002
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