Biochemistry, Biophysics, and Structural Biology Commons^™

The Unavoidable Threat Of Aggregation: Implications For Folding And Function Of A Β-Rich Protein, Mylene Hazelle Anne Ferrolino

Open Access Dissertations

Protein aggregation has been implicated in several catastrophic diseases (neurodegeneration, diabetes, ALS) and its complexity has also become a major obstacle in large-scale production of protein-based therapeutics. Despite the generic behavior of proteins to aggregate, only a few globular proteins have known aggregation mechanisms. At present, there have been no clear connections between a protein folding, function and aggregation. We have tackled the challenge of understanding the links between a protein's natural tendency to fold and function with its propensity to misfold and aggregate. Using a predominantly beta-sheet protein whose in vitro folding has been explored in detail: cellular retinoic …