Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.698907
Title: Assessing the physiological and pathological functions of tissue Transglutaminase using FRET analysis
Author: Sharma, Shruti
ISNI:       0000 0004 5993 3876
Awarding Body: Aston University
Current Institution: Aston University
Date of Award: 2016
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Abstract:
Tissue Transglutaminase (TG2) is a cross-linking enzyme that links proteins by the formation of covalent bonds and confers resistance to proteolytic degradation. TG2 acts as a cell adhesion protein by binding to matrix fibronectin, cell surface heparan sulphates and integrins. TG2 has been implicated in a variety of diseases such as neurodegenerative disease, fibrosis and cancer. However, little is known about the mechanisms involved in its secretion, intracellular or extracellular activation or how these are regulated. The activity of TG2 is tightly controlled by GTP binding and calcium is required for its activation. TG2 assumes two strikingly different conformations, a catalytically inactive compact one in the presence of GTP and an active extended one in the presence of Ca2+. This conformation change affects the functions of TG2 including its transamidating activity, its affinities and juxtaposition of binding sites for fibronectin, heparan sulphates and integrins. To study this, a FRET (Förster Resonance energy Transfer) sensor was constructed using the fluorescent proteins CFP and YFP fused to the N and C terminus of TG2, respectively. The FRET sensor has demonstrated different fluorescent characteristics depending on the conformation of TG2 and was used to monitor the conformational change that is induced by calcium or GTP binding.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.698907  DOI: Not available
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