Focus Day
Tuesday April 11, 2023
9:45 am Chair’s Opening Remarks
Back to the Future with Ubiquitin
10:00 am Targeting Ubiquitination Zones
Synopsis
- Spotlighting the relevance of ubiquitination zones for ligase drug discovery
- Exploring ubiquitination when ubiquitin isn’t the target
10:30 am Sculpting the Ubiquitination Pattern to Ensure Efficient Proteasomal Degradation
Synopsis
- Developing a better understanding of how different ubiquitin modifications influence degradation through the proteasome
- Characterizing how proteasome-bound deubiquitinases regulate the degradation process
- Identifying substrates dependent on deubiquitinase activity for degradation
11:00 am Showcasing the Mechanisms of Substrate Ubiquitination by the Anaphase-Promoting Complex/Cyclosome
Synopsis
- Investigating the Anaphase-Promoting Complex/Cyclosome (APC/C) as a master regulator of cell cycle control
- Dissecting the mechanisms of processive polyubiquitination using cryo-EM
- Uncovering new substrate binding modes and discussing potential implications for other RING E3s
11:30 am PANEL DISCUSSION: Bridging the Knowledge Gap from Ubiquitination to the Proteasome
Synopsis
- Progressing our knowledge gap from ubiquitination to the proteasome
- Identifying whether deubiquitination has occurred and how this impinges on degradation expression levels
12:15 pm Afternoon Networking Break
Navigating E3 Ligase Protein Biology & Structural Functions
1:15 pm Supercharging Our Understanding of E3 Ligases to Enable Substrate Identification
Synopsis
- Harnessing structural biology information of your target ligase to overcome the complexity of studying ligases
- Considering the location of your ligase in the context of the cell cycle and the flexibility of the protein
- Identifying substrates using pull-down assays to check for signatures
1:45 pm INTERACTIVE ROUNDTABLE DISCUSSION
Synopsis
Considering Dynamic Molecular Movement in AI Structures
- Weighing the benefits of static crystal modeling versus current AI/ML approaches to achieving dynamic molecular structures
- What are the current limitations to AI modeling techniques/technologies?
Understanding Structural Dynamics for Large & Moving Molecules
- Design high-resolution structures for large and complex molecules
- Detailing why large molecules have notoriously been difficult to achieve crystal structures for
- Are we any closer with recent technological advancements?
2:45 pm Afternoon Networking Break
3:15 pm Uncovering the Biology & Drug-Ability of an Orphaned Ubiquitin E3 Ligase
Synopsis
- Characterizing an E3 ligase from a structural biology perspective and pathophysiology
- Exploring the downstream effects of degradation of the ligase through protein expression analyses
- Identifying the endogenous substrate for small molecule decision making
3:45 pm Performing Cryo-EM Analyses of the DDB1 CRBN Apo Complex to Demonstrate Functional Insights of Allosteric Regulation of Cereblon
4:15 pm Chair’s Closing Remarks & End of Focus Day
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