Self-Assembly and Sequence Length Dependence on Nanofibrils of Polyglutamine Peptides

Self-Assembly and Sequence Length Dependence on Nanofibrils of Polyglutamine Peptides Publisher Pubmed

Inayathullah M^{1, 6, 11} ; Tan A^{1, 2, 3} ; Jeyaraj R² ; Lam J² ; Cho NJ^{4, 7} ; Liu CW⁵ ; Manoukian MAC⁸ ; Ashkan K⁹ ; Mahmoudi M^{1, 10, 11} ; Rajadas J^{1, 11}

Show Affiliations

1. Biomaterials and oAdvanced Drug Delivery Laboratory (BioADD), Stanford University School of Medicine, Stanford University, Palo Alto, CA, United States
2. UCL Medical School, University College London (UCL), London, United Kingdom
3. University College London Hospitals NHS Foundation Trust, London, United Kingdom
4. Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford University, Palo Alto, CA, United States
5. Stanford Magnetic Resonance Laboratory, Stanford University, Palo Alto, CA, United States
6. Bioorganic and Neurochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai, Tamilnadu, India
7. School of Materials Science and Engineering, Nanyang Technological University, Singapore
8. Department of Dermatology, Stanford University School of Medicine, Stanford University, Palo Alto, CA, United States
9. Department of Neurosurgery, King's College Hospital NHS Foundation Trust, King's College London, London, United Kingdom
10. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
11. Cardiovascular Pharmacology Division, Cardiovascular Institute, Stanford University School of Medicine, Stanford University, Palo Alto, CA, United States

Source: Neuropeptides Published:2016

Abstract

Huntington's disease (HD) is recognized as a currently incurable, inherited neurodegenerative disorder caused by the accumulation of misfolded polyglutamine (polyQ) peptide aggregates in neuronal cells. Yet, the mechanism by which newly formed polyQ chains interact and assemble into toxic oligomeric structures remains a critical, unresolved issue. In order to shed further light on the matter, our group elected to investigate the folding of polyQ peptides - examining glutamine repeat lengths ranging from 3 to 44 residues. To characterize these aggregates we employed a diverse array of technologies, including: nuclear magnetic resonance; circular dichroism; Fourier transform infrared spectroscopy; fluorescence resonance energy transfer (FRET), and atomic force microscopy. The data we obtained suggest that an increase in the number of glutamine repeats above 14 residues results in disordered loop structures, with different repeat lengths demonstrating unique folding characteristics. This differential folding manifests in the formation of distinct nano-sized fibrils, and on this basis, we postulate the idea of 14 polyQ repeats representing a critical loop length for neurotoxicity - a property that we hope may prove amenable to future therapeutic intervention. Furthermore, FRET measurements on aged assemblages indicate an increase in the end-to-end distance of the peptide with time, most probably due to the intermixing of individual peptide strands within the nanofibril. Further insight into this apparent time-dependent reorganization of aggregated polyQ peptides may influence future disease modeling of polyQ-related proteinopathies, in addition to directing novel clinical innovations. © 2016 Elsevier Ltd.

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Style	Citing Format
MLA	Inayathullah M, et al.. "Self-Assembly and Sequence Length Dependence on Nanofibrils of Polyglutamine Peptides." Neuropeptides, vol. 57, no. , 2016, pp. 71-83.
APA	Inayathullah M, Tan A, Jeyaraj R, Lam J, Cho NJ, Liu CW, Manoukian MAC, Ashkan K, Mahmoudi M, Rajadas J (2016). Self-Assembly and Sequence Length Dependence on Nanofibrils of Polyglutamine Peptides. Neuropeptides, 57(), 71-83.
Chicago	Inayathullah M, Tan A, Jeyaraj R, Lam J, Cho NJ, Liu CW, Manoukian MAC, Ashkan K, Mahmoudi M, Rajadas J. "Self-Assembly and Sequence Length Dependence on Nanofibrils of Polyglutamine Peptides." Neuropeptides 57, no. (2016): 71-83.
Harvard	Inayathullah M et al. (2016) 'Self-Assembly and Sequence Length Dependence on Nanofibrils of Polyglutamine Peptides', Neuropeptides, 57(), pp. 71-83.
Vancouver	Inayathullah M, Tan A, Jeyaraj R, Lam J, Cho NJ, Liu CW, et al.. Self-Assembly and Sequence Length Dependence on Nanofibrils of Polyglutamine Peptides. Neuropeptides. 2016;57():71-83.
BibTex	@article{ author = {Inayathullah M and Tan A and Jeyaraj R and Lam J and Cho NJ and Liu CW and Manoukian MAC and Ashkan K and Mahmoudi M and Rajadas J}, title = {Self-Assembly and Sequence Length Dependence on Nanofibrils of Polyglutamine Peptides}, journal = {Neuropeptides}, volume = {57}, number = {}, pages = {71-83}, year = {2016} }
RIS	TY - JOUR AU - Inayathullah M AU - Tan A AU - Jeyaraj R AU - Lam J AU - Cho NJ AU - Liu CW AU - Manoukian MAC AU - Ashkan K AU - Mahmoudi M AU - Rajadas J TI - Self-Assembly and Sequence Length Dependence on Nanofibrils of Polyglutamine Peptides JO - Neuropeptides VL - 57 IS - SP - 71 EP - 83 PY - 2016 ER -

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