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Processing and trafficking of Shiga-like toxin 1 in eukaryotic cells
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Lea, Nicholas (1996) Processing and trafficking of Shiga-like toxin 1 in eukaryotic cells. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b1403810~S1
Abstract
Shiga toxin (ST) and the Escherichia coli Shiga-like toxins (SLTs) are type 11 ribosome inactivating proteins (RIPs). All members of this group exhibit specific RNA N-glycosidase activity, the prototype being the plant toxin ricin. ST and the SL Ts are bipartite toxins composed of a catalytic A subunit and a pentamer of cell binding B subunits. These toxins show overall structural similarities to ricin, which is also a bipartite toxin with a catalytic A chain and a single cell binding B chain. The A chains of ST and SL T 1 show homology to ricin A chain, particularly in the active site region, and appear identical in their enzymatic mechanism. The respective B chains however are structurally very different and interact with quite different cellular components.
In this study, the role of intracellular proteolytic activation of SLT 1 is addressed using a molecular biological approach. The biological characteristics of several mutant SL Ts has been investigated both in vitro, by addition of exogenous protease, and in vivo by comparing the relative cytotoxicities of mutant and wild type proteins in Vero cells. The intracellular processing of these mutant toxins has also been examined. In parallel, the biological properties of a ricin A chain SL T 1 chimeric protein has been investigated. The ultimate aim of this study was to extend our knowledge of the proteolytic processing requirements of SL T 1 and it has led to the conclusion that proteolytic removal ofthe A2 portion of SL T 1 is not an essential prerequisite for intoxication of Vero cells with SLT 1.
| Item Type: | Thesis or Dissertation (PhD) | ||||
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| Subjects: | Q Science > QR Microbiology | ||||
| Official Date: | 1996 | ||||
| Dates: |
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| Institution: | University of Warwick | ||||
| Theses Department: | Department of Biological Sciences | ||||
| Thesis Type: | PhD | ||||
| Publication Status: | Unpublished | ||||
| Supervisor(s)/Advisor: | Roberts, L. M. (Lynne M.) | ||||
| Extent: | iv, 274 leaves : illustrations, charts | ||||
| Language: | eng |
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