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Updated: Feb 28, 2026
11:22
Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy
Published on: June 27, 2018
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Formation and Structure of Wild Type Huntingtin Exon-1 Fibrils.
J Mario Isas1, Andreas Langen1, Myles C Isas1
1Department of Biochemistry and Molecular Medicine, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California , Los Angeles, California, United States.
Biochemistry
|June 17, 2017
Summary
Wild-type huntingtin protein (HTT) fibrils can seed mutant HTT aggregation in Huntington's disease (HD). These wild-type fibrils mimic mutant structures, potentially perpetuating disease pathology.
Area of Science:
- Neurodegenerative diseases
- Molecular biology
- Protein aggregation
Background:
- Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder.
- Mutant huntingtin protein (HTT) forms toxic fibrils, but the role of wild-type HTT is unclear.
Purpose of the Study:
- Investigate the role of wild-type HTT in the formation, propagation, and structure of HTT fibrils in HD.
Main Methods:
- Solid-state Nuclear Magnetic Resonance (NMR)
- Electron Paramagnetic Resonance (EPR) spectroscopy
Main Results:
- Mutant HTT fibrils can seed wild-type HTT aggregation into amyloid fibrils.
- Wild-type HTT fibrils structurally resemble mutant fibrils, with a less extended core.
- Wild-type HTT monomers are more soluble and less prone to fibril incorporation than mutant HTT.
Conclusions:
- Wild-type HTT fibrils can perpetuate the structural characteristics of mutant HTT fibrils in HD.
- This suggests a potential mechanism for disease propagation involving both mutant and wild-type HTT.
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