Post-Translational Protein Switches: Novel and Selective Control in Human Cells
dc.contributor.advisor | Ghosh, Indraneel | |
dc.contributor.author | Sugerman, Samuel Miles | |
dc.creator | Sugerman, Samuel Miles | |
dc.date.accessioned | 2022-08-18T20:33:12Z | |
dc.date.available | 2022-08-18T20:33:12Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Sugerman, Samuel Miles. (2022). Post-Translational Protein Switches: Novel and Selective Control in Human Cells (Doctoral dissertation, University of Arizona, Tucson, USA). | |
dc.identifier.uri | http://hdl.handle.net/10150/665619 | |
dc.description.abstract | Controlling 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.iso | en | |
dc.publisher | The University of Arizona. | |
dc.rights | Copyright © 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.uri | http://rightsstatements.org/vocab/InC/1.0/ | |
dc.subject | domain insertion | |
dc.subject | inducible protein switch | |
dc.subject | protein engineering | |
dc.subject | protein switches | |
dc.subject | protein turn-on | |
dc.subject | split protein | |
dc.title | Post-Translational Protein Switches: Novel and Selective Control in Human Cells | |
dc.type | text | |
dc.type | Electronic Dissertation | |
thesis.degree.grantor | University of Arizona | |
thesis.degree.level | doctoral | |
dc.contributor.committeemember | Charest, Pascale | |
dc.contributor.committeemember | Cordes, Matthew | |
dc.contributor.committeemember | Jewett, John | |
dc.description.release | Release after 08/05/2024 | |
thesis.degree.discipline | Graduate College | |
thesis.degree.discipline | Biochemistry | |
thesis.degree.name | Ph.D. |