Exploring the Interactions Between UBLs and E2s: A Novel Approach for Designing Specific E2 Inhibitors
Poster Number
14B
Format
Poster Presentation
Faculty Mentor Name
Dr. Joseph S. Harrison
Faculty Mentor Department
Department of Chemistry
Abstract/Artist Statement
Ubiquitination of proteins is an essential post-translational regulatory mechanism in cells, crucial to the recycling of short-lived proteins, as well as the degradation of abnormal or damaged proteins. Ubiquitination occurs in a three-step pathway by ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3), resulting in the covalent modification and tagging of a protein with one or more ubiquitin molecules. Following ubiquitination, proteasomes can recognize proteins and degrade them. In addition to ubiquitin, there are ~400 ubiquitin-like domains (UBLs), which are protein domains sharing structural and functional similarities to ubiquitin. Humans also have ~40 E2s that play an important role in the transfer of ubiquitin from E1s to E3/target protein complexes. This study first aimed to characterize various UBLs using biochemical, biophysical, and computational approaches, which involved visualizing changes in the sequence and resulting function of UBLs, as well as comparing UBL sequences using an existing database. The study also aimed to explore the enzymatic activities, regulation, and interactions between E2s and UBLs. A technique central to these characterizations was METRIS (Mechanically Transduced Immunosorbent Assay), which examined both weak and strong interactions between E2s and UBLs. One significant example of these interactions involved the E3 UHRF1, which uses its UBL domain to direct ubiquitin transfer from E2s to histone H3. Histone H3 has been implicated in the regulation of chromatin structure and gene expression via DNA methylation. The interactions between E2s and UBLs provide vital information for designing specific E2 inhibitors and enhance our understanding of the structure, function, sequence, and relationships between UBLs. Ultimately, this research furthers our knowledge of the ubiquitination pathway and its downstream effects.
Location
Information Commons, William Knox Holt Memorial Library and Learning Center
Start Date
29-4-2023 10:00 AM
End Date
29-4-2023 1:00 PM
Exploring the Interactions Between UBLs and E2s: A Novel Approach for Designing Specific E2 Inhibitors
Information Commons, William Knox Holt Memorial Library and Learning Center
Ubiquitination of proteins is an essential post-translational regulatory mechanism in cells, crucial to the recycling of short-lived proteins, as well as the degradation of abnormal or damaged proteins. Ubiquitination occurs in a three-step pathway by ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3), resulting in the covalent modification and tagging of a protein with one or more ubiquitin molecules. Following ubiquitination, proteasomes can recognize proteins and degrade them. In addition to ubiquitin, there are ~400 ubiquitin-like domains (UBLs), which are protein domains sharing structural and functional similarities to ubiquitin. Humans also have ~40 E2s that play an important role in the transfer of ubiquitin from E1s to E3/target protein complexes. This study first aimed to characterize various UBLs using biochemical, biophysical, and computational approaches, which involved visualizing changes in the sequence and resulting function of UBLs, as well as comparing UBL sequences using an existing database. The study also aimed to explore the enzymatic activities, regulation, and interactions between E2s and UBLs. A technique central to these characterizations was METRIS (Mechanically Transduced Immunosorbent Assay), which examined both weak and strong interactions between E2s and UBLs. One significant example of these interactions involved the E3 UHRF1, which uses its UBL domain to direct ubiquitin transfer from E2s to histone H3. Histone H3 has been implicated in the regulation of chromatin structure and gene expression via DNA methylation. The interactions between E2s and UBLs provide vital information for designing specific E2 inhibitors and enhance our understanding of the structure, function, sequence, and relationships between UBLs. Ultimately, this research furthers our knowledge of the ubiquitination pathway and its downstream effects.