Exploring the Interactions Between UBLs and E2s: A Novel Approach for Designing Specific E2 Inhibitors

Poster Number

14B

Lead Author Major

Biological Sciences, Pre-dentistry

Lead Author Status

Junior

Second Author Major

Biochemistry

Second Author Status

Senior

Third Author Major

Biological Sciences

Third Author Status

Senior

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

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Apr 29th, 10:00 AM Apr 29th, 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.