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dc.contributor.advisorGhosh, Indraneel
dc.contributor.authorSugerman, Samuel Miles
dc.creatorSugerman, Samuel Miles
dc.date.accessioned2022-08-18T20:33:12Z
dc.date.available2022-08-18T20:33:12Z
dc.date.issued2022
dc.identifier.citationSugerman, Samuel Miles. (2022). Post-Translational Protein Switches: Novel and Selective Control in Human Cells (Doctoral dissertation, University of Arizona, Tucson, USA).
dc.identifier.urihttp://hdl.handle.net/10150/665619
dc.description.abstractControlling enzymes in a monospecific fashion is significant in the study and treatment of metabolic diseases and is a fundamental scientific investigation. There exists a gap in our ability to isolate the function of any one protein within complex signaling networks. We lack adequate tools to specifically probe a single protein functioning in a dynamic network without off-target interactions or crosstalk with other cellular proteins.Here, we present two turn-on switches to interrogate protein signaling pathways. The first switch is a domain insertion turn-on switch that we engineer toward selective interactions. In the process, we highlight discrepancies between observed selectivity in vitro and a lack of correlation in the specificity within cellular environments. The second switch is a first-in-class chemically-induced dimerization complex that we use to reassemble split enzymes. Both switches are built using the protein Bcl-xL. Our last pursuit is to generate a Bcl-xL phage-displayed library that can be used to select for potentially-novel interactions with BH3 peptide binding partners. We hypothesize that there is potential to engineer selective protein switches within human cells based on these technologies.
dc.language.isoen
dc.publisherThe University of Arizona.
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectdomain insertion
dc.subjectinducible protein switch
dc.subjectprotein engineering
dc.subjectprotein switches
dc.subjectprotein turn-on
dc.subjectsplit protein
dc.titlePost-Translational Protein Switches: Novel and Selective Control in Human Cells
dc.typetext
dc.typeElectronic Dissertation
thesis.degree.grantorUniversity of Arizona
thesis.degree.leveldoctoral
dc.contributor.committeememberCharest, Pascale
dc.contributor.committeememberCordes, Matthew
dc.contributor.committeememberJewett, John
dc.description.releaseRelease after 08/05/2024
thesis.degree.disciplineGraduate College
thesis.degree.disciplineBiochemistry
thesis.degree.namePh.D.


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