Unraveling the Regulation of Plant and Yeast Plastin Proteins: A Structural Determination Study
| dc.contributor.advisor | Haji-Ghassemi, Omid | |
| dc.contributor.advisor | Vogel, Hans J. | |
| dc.contributor.author | Khassan, Oleg | |
| dc.contributor.committeemember | Fraser, Marie E. | |
| dc.contributor.committeemember | Williams, Gareth J. | |
| dc.date | 2025-06 | |
| dc.date.accessioned | 2025-01-30T15:41:22Z | |
| dc.date.available | 2025-01-30T15:41:22Z | |
| dc.date.issued | 2025-01-25 | |
| dc.description.abstract | L-plastin is a 70 kDa protein normally found in white blood cells, where it plays a pivotal role in the formation of actin-rich protrusions required for cell motility. Interestingly, many cancers hijack the white blood cell’s ability to move around and transform into metastatic cancers by upregulating L-plastin. Despite the potential clinical implications of this protein, the function and regulation of L-plastin remain enigmatic, and its full-length structure has yet to be fully characterized. By elucidating the regulatory mechanism of this proposed cancer biomarker, we may find a new approach to manipulate it and thereby reduce the motility of metastatic cancers. Regulation of the actin-bundling activity of L-plastin has been presumed to involve a structural change brought about by the binding of calcium to the N-terminal calcium-binding region (EF-hands). Intriguingly, in plants and yeast this region seems to be conserved, and yet incapable of sensing calcium. This implies another calcium-sensing mechanism may be involved in its regulation. To gain deeper insights into the regulation of L-plastin, we investigated the EF-hands to identify potential proteins involved in modulating its activity and elucidated the structures of the EF-hands of plant and yeast plastins using X-ray crystallography. Using nuclear magnetic resonance (NMR), we uncovered a calcium-sensing protein, calmodulin (CaM), involved in binding and potentially regulating L-plastin. The high-resolution studies of the EF-hands in plants and yeast suggest unique regulatory mechanisms that could enable plant and yeast plastins to function autonomously, independent of calcium. Identifying new mechanisms for actin-bundling can have a significant impact on the advancement of drug-development for the treatment of metastatic cancers. | |
| dc.identifier.citation | Khassan, O. (2025). Unraveling the regulation of plant and yeast plastin proteins: a structural determination study (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | |
| dc.identifier.uri | https://hdl.handle.net/1880/120616 | |
| dc.language.iso | en | |
| dc.publisher.faculty | Graduate Studies | |
| dc.publisher.institution | University of Calgary | |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject.classification | Education--Sciences | |
| dc.subject.classification | Biochemistry | |
| dc.title | Unraveling the Regulation of Plant and Yeast Plastin Proteins: A Structural Determination Study | |
| dc.type | master thesis | |
| thesis.degree.discipline | Biological Sciences | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Master of Science (MSc) | |
| ucalgary.thesis.accesssetbystudent | I require a thesis withhold – I need to delay the release of my thesis due to a patent application, and other reasons outlined in the link above. I have/will need to submit a thesis withhold application. |