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Full-Text Articles in Life Sciences
Factors That Contribute To De Novo Protein Misfolding And Prion Formation In Saccharomyces Cerevisiae, Kathryn Morgan Keefer
Factors That Contribute To De Novo Protein Misfolding And Prion Formation In Saccharomyces Cerevisiae, Kathryn Morgan Keefer
Arts & Sciences Electronic Theses and Dissertations
Protein misfolding is a common phenomenon that can have severe consequences on cellular and organismal health. Despite this, the causes of protein misfolding remain poorly understood. Prions are a class of proteins that, when misfolded, can convert other molecules into a heritable, non-native conformation. The yeast Saccharomyces cerevisiae naturally harbors several diverse prion-forming proteins; thus, it is an ideal model with which to investigate the factors that influence misfolding and aggregation.This thesis utilizes the yeast prions [PSI+] and [RNQ+] to investigate two distinct steps of the protein misfolding pathway: interactions with chaperones and their cofactors, and heterologous templating by other …
Quantification Of Conformational Heterogeneity And Its Role In Protein Aggregation And Unfolding, Nicholas J. Lyle
Quantification Of Conformational Heterogeneity And Its Role In Protein Aggregation And Unfolding, Nicholas J. Lyle
Arts & Sciences Electronic Theses and Dissertations
Proteins can exhibit significant conformational heterogeneity either under denaturing conditions or in aqueous solutions. The latter is true for a class of proteins whose sequences predispose them to form heterogeneous ensembles of conformations. Characterization of conformational heterogeneity in a protein ensemble requires the quantification of the amplitudes of spontaneous fluctuations in conjunction with information regarding coarse grain measures that report on the average sizes, shapes, and densities. This often demands multiplexed experimental approaches whose readouts are interpreted or annotated using ensembles drawn from atomistic or coarse grain computational simulations. Efforts to characterize conformational heterogeneity contribute directly to our understanding of …