Thesis
Regulation of BORG2 by Cdc42 through disruption of internal structure
Master of Science (M.S.), Drexel University
Jul 2024
DOI:
https://doi.org/10.17918/00010502
Abstract
The Binder of Rho GTPases (BORG)/CDC42 effector proteins (CDC42EP) family has been associated with multiple cellular processes and diseases. The family comprises five Rho GTPase binding proteins, but we focus here on BORG2. Despite BORG2's emerging role in actin dynamics and various cancers, it is poorly understood at the structure-function level. BORG2 contains two well-known domains separated by what is expected to be a disordered region. The CRIB (CDC42/Rac Interactive Binding) domain binds to CDC42 (Cell Division Control protein 42 homolog), while the BORG homology 3 (BH3) domain binds to the septin family of GTPases. Though these domains can bind their partners independently, our biochemical work found that binding is negatively cooperative: that the binding of a ligand to one site decreases the affinity for subsequent ligand binding at other sites. We focus on finding the structural differences and proof of internal interactions within BORG2 that indicate broader functional and regulatory mechanisms for the family. Multiple fluorescent spectroscopic probes were used to show a novel N- and C-terminal interaction disrupted upon CDC42-GTP (active CDC42) binding.
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Details
- Title
- Regulation of BORG2 by Cdc42 through disruption of internal structure
- Creators
- Priyashree Nagarajan
- Contributors
- Shae B. Padrick (Advisor)Christian Sell (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- ix, 118 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 991021899615204721