Wild-type hen egg white lysozyme aggregation in vitro can form self-seeding amyloid conformational variants

Sivalingam, V and Prasanna, N L and Sharma, N and Prasad, A and Patel, Basant Kumar (2016) Wild-type hen egg white lysozyme aggregation in vitro can form self-seeding amyloid conformational variants. Biophysical Chemistry, 219. pp. 28-37. ISSN 0301-4622

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Misfolded β-sheet-rich protein aggregates termed amyloid, deposit in vivo leading to debilitating diseases such as Alzheimer's, prion and renal amyloidosis diseases etc. Strikingly, amyloid can induce conversion of their natively folded monomers into similarly aggregated conformation via ‘seeding’. The specificity of seeding is well documented in vivo for prions, where prion-variants arising from conformationally altered amyloids of the same protein, faithfully seed monomers into amyloid displaying the original variant's conformation. Thus far, amyloid variant formation is reported only for a few non-prion proteins like Alzheimer's Aβ42-peptide and β-2 microglobulin, however, their conformational cross-seeding capabilities are unexplored. While mutant human lysozyme causes renal amyloidosis, the hen egg white lysozyme (HEWL) has been extensively investigated in vitro as a model amyloid protein. Here we investigated if wild-type HEWL could form self-seeding amyloid variants to examine if variant formation is more wide-spread. We found that HEWL aggregates formed under quiescent versus agitated conditions, displayed different particle sizes, detergent stabilities & β-sheet content, and they only seeded monomeric HEWL under similar incubation conditions, but not under swapped incubation conditions thereby showing amyloid variant formation by HEWL analogous to prion variants. This may have implications to the amyloidosis caused by different mutants of human lysozyme.

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IITH Creators:
IITH CreatorsORCiD
Patel, Basant Kumarhttp://orcid.org/0000-0001-9465-4803
Item Type: Article
Additional Information: Senior research fellowship (SRF) from University Grants Commission (UGC), Govt. of India to Mr. Vishwanath S. and SRF from Ministry of Human Resource Deve lopment (MHRD), Govt. of India to Neetu Sharma & Archana Prasad , are duly acknowledged. Nalla Lakshmi Prasanna thanks MHRD for research assistant fellowship. We thank IIT - Hyderabad funded by MHRD, Govt. of India for research consumable and infrastructural support. We sincerely thank Dr. C. S. Sharma, Dr. R . Ramadurai , Mr. J . Joseph, & Mr. K. Miriyala from IIT - Hyderabad , for help with AFM imaging. We also thank Dr. S . Mazumdar and Mr. U . Bhutani from Dept. of Chemical Engineering, IIT - Hyderabad , for help with the DLS data acquisition
Uncontrolled Keywords: Amyloid; Hen egg white lysozyme; Amyloid variants; AFM; Dynamic light scattering
Subjects: Others > Biochemistry
Others > Biotechnology
Divisions: Department of Biotechnology
Depositing User: Team Library
Date Deposited: 03 Oct 2016 05:16
Last Modified: 10 Nov 2017 06:39
URI: http://raiith.iith.ac.in/id/eprint/2788
Publisher URL: https://doi.org/10.1016/j.bpc.2016.09.009
OA policy: http://www.sherpa.ac.uk/romeo/issn/0301-4622/
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