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BIOPHYSICAL STUDIES OF UBIQUITIN: FROM FOLDING TO PROTEIN ENGINEERING

dc.contributor.advisorFushman, Daviden_US
dc.contributor.authorCamara, Christina Men_US
dc.date.accessioned2022-02-04T06:39:20Z
dc.date.available2022-02-04T06:39:20Z
dc.date.issued2021en_US
dc.identifierhttps://doi.org/10.13016/xdef-86uy
dc.identifier.urihttp://hdl.handle.net/1903/28461
dc.description.abstractThe signaling protein ubiquitin is known for its ubiquity — existing in nearly all cel- lular compartments, holding a prominent role in major cellular signaling pathways and serving as a model system for protein folding. Herein, we honor this stature by exploring several aspects of the ubiquitin system form biophysical, structural, and computational per- spectives. Our efforts begin from the standpoint of protein engineering, where we extend ubiquitin’s function by installing a transition–metal binding motif and elevate it to the sta- tus of a metalloprotein. In doing so, we introduce novel spectroscopic behaviors, reactive propensities, and the capability to form non–canonical polyubiquitin chains — with appli- cations that span from molecular nanotechnology to synthetic biology. We then shift to foundational investigations of ubiquitin’s fold. By characterizing local degrees of freedom, we demonstrate how conformational motions of ubiquitin’s C–terminus can be controlled by the cellular microenvironment. This response, in turn, can regulate molecular recog- nition within the ubiquitination cascade. Finally, we approach global aspects of ubiquitin folding — exploring how a motif containing the C–terminus and the β5 strand might assem- ble into ubiquitin’s β –grasp architecture — with general lessons for ubiquitin–like proteins and other systems with an apparent two–state folding mechanism.en_US
dc.language.isoenen_US
dc.titleBIOPHYSICAL STUDIES OF UBIQUITIN: FROM FOLDING TO PROTEIN ENGINEERINGen_US
dc.typeDissertationen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.contributor.departmentBiochemistryen_US
dc.subject.pqcontrolledBiochemistryen_US
dc.subject.pqcontrolledBiophysicsen_US
dc.subject.pqcontrolledPhysical chemistryen_US
dc.subject.pquncontrolledProtein Engineeringen_US
dc.subject.pquncontrolledUbiquitinen_US


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