Characterization of Tumor Overexpressed Gene (TOG) Domains 3 and 5 of XMAP215 Family Proteins
Public Deposited- Last Modified
- February 26, 2019
- Creator
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Stevens, Olivia
- Affiliation: College of Arts and Sciences, Department of Chemistry
- Abstract
- The inherent differences in TOG domain architectures and their affect on MT dynamics provoke two separate questions. The first is in regards to whether the TOG domains are similar or different in their functionality, and the second concerns the type of tubulin-binding mechanism utilized by the TOG domain array. I hypothesize that TOG domain architectures comprising XMAP215 TOG domain arrays are arranged in a specific orientation to distinguish between different tubulin structural states, which may play an important mechanistic role in XMAP215-mediated MT polymerization. To study this hypothesis, I am going to determine if TOG domain structures are conserved between XMAP215 family members, test the role of different TOG domain features in promoting domain stabilization, and understand how different TOG architectures affect MT polymerization. These studies will be achieved by (1) structurally characterizing TOG domains 3 and 5 from species across the XMAP215 family by X-ray crystallography, (2) completing the Msps TOG array by crystallizing Msps TOG1 (3) probing the role of TOG5’s extra N-terminal HR in promoting secondary structure and domain stability by creating mutant constructs and performing comparative circular dichroism studies, and (4) examining the effects of intra-HR loop A W→E (TOG3) and F→E (TOG5) mutations on the catalysis of MT polymerization by these TOG domains in a light scattering assay. Collectively, these experiments will provide further comprehension of the mechanism of XMAP215 proteins and will provide insight into how the architecture and structural elements of arrayed TOG domains dictate their functionality and differential contribution to MT dynamics.
- Date of publication
- spring 2015
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- Rights statement
- In Copyright
- Note
- Funding: None
- Advisor
- Slep, Kevin
- Degree
- Bachelor of Science
- Honors level
- Honors
- Degree granting institution
- University of North Carolina at Chapel Hill
- Extent
- 16
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