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DC Field | Value | Language |
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dc.contributor.advisor | Whitney, John | - |
dc.contributor.author | Grebenc, Dirk | - |
dc.date.accessioned | 2024-01-29T19:46:16Z | - |
dc.date.available | 2024-01-29T19:46:16Z | - |
dc.date.issued | 2024-12 | - |
dc.identifier.uri | http://hdl.handle.net/11375/29454 | - |
dc.description | This thesis presents two crystal structures of a novel family of putative chaperone proteins associated with the Type VII Secretion System of Streptococcus, and other Firmicutes species. | en_US |
dc.description.abstract | Bacteria interact with their environment using sophisticated protein export pathways. The type VII secretion system (T7SS) is a membrane-bound ATP- dependent protein translocase found throughout the Gram-positive phyla Actinobacteria and Firmicutes, where it is referred to as T7SSa and T7SSb, respectively. Most studies on the T7SSb system focus on its role in bacterial competition. The T7SSb secretes polymorphic antibacterial toxins that contain an α-helical domain belonging to the Leucine-X-Glycine (LXG) protein family. LXG proteins are genetically encoded next to two small LXG-associated α-helical proteins (Laps). We have recently demonstrated that Laps form a heterotrimeric complex with their cognate T7SS toxin. However, the molecular details governing LXG toxin recognition and recruitment to the T7SSb apparatus remain incomplete. The domain of unknown function (DUF) 4176 protein family is found within certain Lap and LXG encoding operons. DUF4176s stand out from the Laps due to their predicted globular shape but are similarly required for the secretion of their associated LXG effector. Interestingly, globular chaperones have previously been described for Mycobacterial T7SSa systems, suggesting that they may be an overlooked feature required for the export of T7SSb effectors as well. In this work, I demonstrate that DUF4176 genes commonly co-occur with LXG and other T7SSb-associated proteins and present the first crystal structures of two DUF4176 proteins from Streptococcus intermedius. I identify surface exposed features on these structures that may be involved in protein-protein interactions and explore possible models for how DUF4176 facilitate the secretion of LXG toxins through the T7SSb. | en_US |
dc.language.iso | en | en_US |
dc.subject | structural biology, protein secretion, bacteriology, bioinformatics, type vii secretion system | en_US |
dc.title | THE STRUCTURE OF A PUTATIVE TYPE VIIb SECRETION SYSTEM CHAPERONE PROTEIN FAMILY | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Biochemistry and Biomedical Sciences | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
dc.description.layabstract | While bacteria are a relatively simple form of life, they are capable of impressively complex behaviours. Many bacteria possess a type of intricate cellular machinery known as secretion systems that allow them to release toxic proteins for competition with other bacteria, which can often lead to infectious disease. The process of generating a protein toxin and secreting it from the cell is highly complex at the molecular level. In other characterized examples, one part of the toxin acts as a signal that is recognized by a specific secretion system whereas the other part harbours the toxic activity. Signal regions are often unstable and require other partner proteins called chaperones or targeting factors to stay together before they are secreted. The Type VII Secretion System (T7SS) is found in bacteria such as Streptococcus and Mycobacterium tuberculosis. The domain of unknown function (DUF) 4176 protein family is a mysterious group of proteins that we hypothesize are important for the secretion of specific toxins by the T7SS. To gain insight into potential functions of DUF4176, I solved two crystal structures of these proteins and examined their three-dimensional architecture. I found specific features on the protein surface that hint at how they might help LXG toxins get secreted by the bacterial machinery. These structural insights lay the groundwork for future experiments probing the role of DUF4176 proteins within the Type VII Secretion System, and sheds further light on hidden complexities of bacterial warfare. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Grebenc_Dirk_W_December2023_MSc.pdf | 13 MB | Adobe PDF | View/Open |
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