Huntingtin fibrils with different toxicity, structure, and seeding potential can be interconverted

J. Mario Isas; Nitin K. Pandey; Hui Xu; Kazuki Teranishi; Alan K. Okada; Ellisa K. Fultz; Anoop Rawat; Anise Applebaum; Franziska Meier; Jeannie Chen; Ralf Langen; Ansgar B. Siemer

doi:10.1038/s41467-021-24411-2

Nature Communications (Jul 2021)

Huntingtin fibrils with different toxicity, structure, and seeding potential can be interconverted

J. Mario Isas,
Nitin K. Pandey,
Hui Xu,
Kazuki Teranishi,
Alan K. Okada,
Ellisa K. Fultz,
Anoop Rawat,
Anise Applebaum,
Franziska Meier,
Jeannie Chen,
Ralf Langen,
Ansgar B. Siemer

Affiliations

J. Mario Isas: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California
Nitin K. Pandey: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California
Hui Xu: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California
Kazuki Teranishi: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California
Alan K. Okada: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California
Ellisa K. Fultz: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California
Anoop Rawat: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California
Anise Applebaum: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California
Franziska Meier: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California
Jeannie Chen: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California
Ralf Langen: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California
Ansgar B. Siemer: Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California

DOI: https://doi.org/10.1038/s41467-021-24411-2
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 11

Abstract

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Huntingtin exon-1 (HTTex1) consists of a N-terminal N17 domain, the disease causing polyQ domain and a C-terminal proline-rich domain (PRD). Here, the authors combine electron paramagnetic resonance (EPR), solid-state NMR with other biophysical method to characterise the structural differences of various HTTex1 fibril types with different toxicity and find that the dynamics and entanglement of the PRD domain differs among them and that the HTTex1 fibrils can be interconverted.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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