1,721,008 research outputs found
Physiological, pathological, and structural implications of non-enzymatic protein-protein interactions of the multifunctional human transglutaminase 2
No full textTransglutaminase 2 (TG2) is a ubiquitously expressed member of an enzyme family catalyzing Ca2+-dependent transamidation of proteins. It is a multifunctional protein having several well-defined enzymatic (GTP binding and hydrolysis, protein disulfide isomerase, and protein kinase activities) and non-enzymatic (multiple interactions in protein scaffolds) functions. Unlike its enzymatic interactions, the significance of TG2's non-enzymatic regulation of its activities has recently gained importance. In this review, we summarize all the partners that directly interact with TG2 in a non-enzymatic manner and analyze how these interactions could modulate the crosslinking activity and cellular functions of TG2 in different cell compartments. We have found that TG2 mostly acts as a scaffold to bridge various proteins, leading to different functional outcomes. We have also studied how specific structural features, such as intrinsically disordered regions and embedded short linear motifs contribute to multifunctionality of TG2. Conformational diversity of intrinsically disordered regions enables them to interact with multiple partners, which can result in different biological outcomes. Indeed, ID regions in TG2 were identified in functionally relevant locations, indicating that they could facilitate conformational transitions towards the catalytically competent form. We reason that these structural features contribute to modulating the physiological and pathological functions of TG2 and could provide a new direction for detecting unique regulatory partners. Additionally, we have assembled all known anti-TG2 antibodies and have discussed their significance as a toolbox for identifying and confirming novel TG2 regulatory functions
"Tissue" transglutaminase is specifically expressed in neonatal rat liver cells undergoing apoptosis upon epidermal growth factor-stimulation.
No full textAmine donor protein substrates for transglutaminase activity in Caenorhabditis elegans.
No full textMadi A, Hoffrogge R, Blasko B, Glocker MO, Fesus L. Amine donor protein substrates for transglutaminase activity in Caenorhabditis elegans. Biochemical and Biophysical Research Communications. 2004;315(4):1064-1069
Expression of tissue transglutaminase in Balb-C 3T3 fibroblasts: effects on cellular morphology and adhesion
No full textIn vivo and in vitro induction of 'tissue' transglutaminase in rat hepatocytes by retinoic acid.
No full textIdentification of a specific one amino acid change in recombinant human transglutaminase 2 that regulates its activity and calcium sensitivity
No full textTG2 (transglutaminase 2) is a calcium-dependent protein crosslinking enzyme which is involved in a variety of cellular processes. The threshold level of calcium needed for endogenous and recombinant TG2 activity has been controversial, the former being more sensitive to calcium than the latter. In the present study we address this question by identifying a single amino acid change from conserved valine to glycine at position 224 in recombinant TG2 compared with the endogenous sequence present in the available genomic databases. Substituting a valine residue for Gly224 in the recombinant TG2 increased its calcium-binding affinity and transamidation activity 10-fold and isopeptidase activity severalfold, explaining the inactivity of widely used recombinant TG2 at physiological calcium concentrations. ITC (isothermal titration calorimetry) measurements showed 7-fold higher calcium-binding affinities for TG2 valine residues which could be activated inside cells. The two forms had comparable substrate- and GTP-binding affinities and also bound fibronectin similarly, but coeliac antibodies had a higher affinity for TG2 valine residues. Structural analysis indicated a higher stability for TG2 valine residues and a decrease in flexibility of the calciumbinding loop resulting in improved metal-binding affinity. The results of the present study suggest that Val224 increases TG2 activity by modulating its calcium-binding affinity enabling transamidation reactions inside cells. © 2013 Biochemical Society
Computational analyses of the effect of novel amino acid clusters of human transglutaminase 2 on its structure and function
No full textTransglutaminase 2 (TGM2) is a unique protein of a nine member family with several enzymatic and non-enzymatic activities and interacting partners. Its physiological and pathological roles, however, are not fully understood. Comparative genomic and computational analysis reported here have revealed phylogenetic changes of TGM2 resulting in novel amino acid clusters in humans and other primates, which may impact secondary structure and increase protein stability. These clusters are located in intrinsically disordered regions and via short linear motifs influence interactions with TGM2 partners directly, or through post-translation modification (phosphorylation and N-glycosylation sites). Our data shed new light on the structural background and evolution of TGM2 multi-functionality and points to so far unrevealed biological roles of the enzyme
The expression of 'tissue' transglutaminase in two human cancer cell lines is related with the programmed cell death (apoptosis)
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