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Ashutosh Tiwari
Department of Chemistry
Michigan Technological University

Protein instability, aggregation, and toxicity: Disulfide-bond integrity holds the key

Protein aggregates are hallmark of several age related disorders including neurodegenerative diseases such as Amyotrophic Lateral Sclerosis, Alzheimer’s and Parkinson’s disease. However, the underlying mechanisms by which these aggregated proteins impair cellular functions and cause toxicity is not clear. Understanding the principles and contributing factors that are expected to regulate protein misfolding, surface hydrophobic exposure, aberrant interactions, or aggregation is key to understanding its relationship to cellular toxicity. I will discuss results from my laboratory wherein we took three proteins and studied their biochemical and biophysical properties in cellular reducing environment and also measured cytotoxicity of the distinct aggregates in cell lines.

References:

Yang M, Dutta C, and Tiwari A. Disulfide-Bond Scrambling Promotes Amorphous Aggregates in Lysozyme and Bovine Serum Albumin. J. Phys. Chem. B (2015) 119(10): 3969-3981. DOI: 10.1021/acs.jpcb.5b00144. PMID: 25689578

Dutta C, Yang M, Long F, Shahbazian-Yassar R, and Tiwari A. Preformed Seeds Modulate Native Insulin Aggregation Kinetics. J. Phys. Chem. B (2015) 119(49): 15089-15099. DOI: 10.1021/acs.jpcb.5b07221. PMID: 26560632

Dorh N, Zhu S, Dhungana KB, Pati R, Luo FT, Liu H, Tiwari A. BODIPY-Based Fluorescent Probes for Sensing Protein Surface-Hydrophobicity. Sci Rep. (2015) 5:18337. DOI: 10.1038/srep18337. PMID: 26679512