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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Principles Of Aaa+ Proteases, Samar Mahmoud
Principles Of Aaa+ Proteases, Samar Mahmoud
Doctoral Dissertations
ATPases associated with diverse cellular activities (AAA+) proteases in bacteria help maintain protein homeostasis by degrading misfolded and regulatory proteins. While a handful of protein targets for these proteases have been identified in Caulobacter crescentus and other organisms, more research is needed to elucidate mechanisms that govern substrate specificity. In the second chapter of this thesis, I will elaborate on how AAA+ substrate specificity is less rigid than previous work has suggested and how limiting ATP or mutations can alter substrate preferences of the ClpXP protease. In the third chapter, I will highlight our efforts to use a quantitative proteomics …
Characterizing The Multifaceted Roles Of The Proteasomal Deubiquitinase Uch37 In Proteostasis, Heather A. Bisbee
Characterizing The Multifaceted Roles Of The Proteasomal Deubiquitinase Uch37 In Proteostasis, Heather A. Bisbee
Doctoral Dissertations
Cellular protein pools are maintained through the biological processes of synthesis, degradation and quality control. As the dysregulation of these processes has been implicated in diseases such as neurodegeneration and cancer, understanding their functions is critical for drug development. Modification of proteins with ubiquitin may direct them to the proteasome, a large cellular protease complex, for degradation. Yet, the proteasome contains three deubiquitinating enzymes (DUBs) which remove ubiquitin from proteins, potentially altering their fate. As each DUB recognizes specific ubiquitin linkages and architectures, their activity may regulate how the proteasome handles substrates in dynamic cellular contexts. In this work, we …
Mechanistic Insights Into Diverse Protease Adaptor Functions, Nathan J. Kuhlmann
Mechanistic Insights Into Diverse Protease Adaptor Functions, Nathan J. Kuhlmann
Doctoral Dissertations
Protein degradation is an essential cellular process that helps maintain proper homeostasis. The ClpXP protease broadly regulates bacterial development and quality control during the cell cycle. The range and order of substrates that ClpXP degrades during the cell cycle is dictated by 3 accessory proteins, which are known as adaptors. This thesis will elaborate on how dimerization tightly regulates the stability and activity of the adaptor protein at the center of this hierarchy, RcdA, and show how this affects normal cellular processes in Caulobacter crescentus. I will discuss the mechanism by which dimerization limits RcdA activity and how the dimerization …