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The Unavoidable Threat Of Aggregation: Implications For Folding And Function Of A Β-Rich Protein, Mylene Hazelle Anne Ferrolino
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 …
Components Of A Protein Machine: Allosteric Domain Assembly And A Disordered C-Terminus Enable The Chaperone Functions Of Hsp70, Robert G. Smock
Components Of A Protein Machine: Allosteric Domain Assembly And A Disordered C-Terminus Enable The Chaperone Functions Of Hsp70, Robert G. Smock
Open Access Dissertations
Hsp70 molecular chaperones protect proteins from aggregation, assist in their native structure formation, and regulate stress responses in the cell. A mechanistic understanding of Hsp70 function will be necessary to explain its physiological roles and guide the therapeutic modulation of various disease states. To this end, several fundamental features of the Hsp70 structure-function relationship are investigated. The central component of Hsp70 chaperone function is its capacity for allosteric signaling between structural domains and tunable binding of misfolded protein substrates. In order to identify a cooperative network of sites that mediates interdomain allostery within Hsp70, a mutational correlation analysis is performed …