Transglutaminases: nature’s biological glues. Biochem J

Department of Life Sciences, Nottingham Trent University, Nottingham, U.K.
Biochemical Journal (Impact Factor: 4.4). 01/2003; 368(Pt 2):377-96. DOI: 10.1042/BJ20021234
Source: PubMed


Transglutaminases (Tgases) are a widely distributed group of enzymes that catalyse the post-translational modification of proteins by the formation of isopeptide bonds. This occurs either through protein cross-linking via epsilon-(gamma-glutamyl)lysine bonds or through incorporation of primary amines at selected peptide-bound glutamine residues. The cross-linked products, often of high molecular mass, are highly resistant to mechanical challenge and proteolytic degradation, and their accumulation is found in a number of tissues and processes where such properties are important, including skin, hair, blood clotting and wound healing. However, deregulation of enzyme activity generally associated with major disruptions in cellular homoeostatic mechanisms has resulted in these enzymes contributing to a number of human diseases, including chronic neurodegeneration, neoplastic diseases, autoimmune diseases, diseases involving progressive tissue fibrosis and diseases related to the epidermis of the skin. In the present review we detail the structural and regulatory features important in mammalian Tgases, with particular focus on the ubiquitous type 2 tissue enzyme. Physiological roles and substrates are discussed with a view to increasing and understanding the pathogenesis of the diseases associated with transglutaminases. Moreover the ability of these enzymes to modify proteins and act as biological glues has not gone unnoticed by the commercial sector. As a consequence, we have included some of the present and future biotechnological applications of this increasingly important group of enzymes.

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Available from: Martin Griffin, Jan 06, 2015
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    • "In humans, transglutaminase 2 (tissue transglutaminase, tTG), is ubiquitously expressed and has multiple functions supplemental to its protein crosslinking ability such as GTPase, ATPase and protein kinase activities (Wang and Griffin, 2011). tTG is primarily recognised as the major autoantigen of the gluten-sensitive enteropathy, coeliac disease (CD), but has been implicated in numerous pathological processes including fibrosis, atherosclerotic plaque formation and metastasis of cancerous cells (Griffin et al., 2002). "
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    ABSTRACT: Antibodies of the IgA class directed against the enzyme tissue transglutaminase (tTG) are highly specific for coeliac disease (CD). IgG antibodies to tTG also occur in CD, and have also been reported in autoimmune diseases such as type 1 diabetes mellitus and Crohn's disease. In comparison to the IgA anti-tTG response, little is known of the IgG anti-tTG response in terms of epitope specificity and IgG subclass usage. The aim of this study was to investigate and compare epitopes recognised by CD and non-CD IgG anti-tTG antibodies, and determine the relative proportions of the IgG subclasses comprising this response. IgG anti-tTG positive individuals who did not have CD were identified by screening groups of patients with type I diabetes mellitus, Crohn's disease and granulomatosis with polyangiitis. Results from ELISA blocking experiments and mutant tTG antigens demonstrate that non-CD IgG anti-tTG bind different epitopic determinants to CD IgG anti-tTG. The IgG subclass usage of coeliac disease and type 1 diabetes was dominated by IgG1, whereas this IgG subclass was infrequently a component of the IgG anti-tTG response in diseases such as granulomatosis with polyangiitis and Crohn's disease. The differences in epitope specificity and subclass usage of IgG anti-tTG observed between CD and non-CD individuals may be due to the differing mechanisms underlying tTG autoimmunity. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Molecular Immunology 07/2015; 67(2 Pt B). DOI:10.1016/j.molimm.2015.06.026 · 2.97 Impact Factor
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    • "Transglutaminases are a family of enzymes that catalyse covalent bond formation between lysine and glutamine-residues in target proteins leading to their post-translational modification [1]. TG2 is the most widely expressed family member [2] and is found both in the cytoplasm and extracellularly at the cell surface [3]. "
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    ABSTRACT: Tissue transglutaminase (TG2) is a multifunctional protein cross-linking enzyme that has been implicated in apoptotic cell clearance but is also important in many other cell functions including cell adhesion, migration and monocyte to macrophage differentiation. Cell surface-associated TG2 regulates cell adhesion and migration, via its association with receptors such as syndecan-4 and β1 and β3 integrins. Whilst defective apoptotic cell clearance has been described in TG2-deficient mice, the precise role of TG2 in apoptotic cell clearance remains ill-defined. Our work addresses the role of macrophage extracellular TG2 in apoptotic cell corpse clearance. Here we reveal TG2 expression and activity (cytosolic and cell surface) in human macrophages and demonstrate that inhibitors of protein crosslinking activity reduce macrophage clearance of dying cells. We show also that cell-impermeable TG2 inhibitors significantly inhibit the ability of macrophages to migrate and clear apoptotic cells through reduced macrophage recruitment to, and binding of, apoptotic cells. Association studies reveal TG2–syndecan-4 interaction through heparan sulphate side chains, and knockdown of syndecan-4 reduces cell surface TG2 activity and apoptotic cell clearance. Furthermore, inhibition of TG2 activity reduces crosslinking of CD44, reported to augment AC clearance. Thus our data define a role for TG2 activity at the surface of human macrophages in multiple stages of AC clearance and we propose that TG2, in association with heparan sulphates, may exert its effect on AC clearance via a mechanism involving the crosslinking of CD44.
    Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 01/2015; 1853(1-1):201-212. DOI:10.1016/j.bbamcr.2014.09.020 · 5.02 Impact Factor
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    • "enzyme and the commercial enzyme [3]. The optimum temperature for enzymatic activity is 55℃; it maintained full activity for 10 min at 40℃, but lost activity within a few minutes at 70℃; and it was active at 10℃, and retained some activity at near-freezing temperatures [1]. MTGases can catalyze acyl transfer by forming covalent crosslinks among proteins, peptides, and primary amines. "
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    ABSTRACT: Transglutaminase (TGase) has been used in food industry since it reconstitutes small meat pieces into a steak. In addition, its application in pharmaceutical industry is well investigated and still under further study. However, the application of TGases in textile and leather industry was minimal before a decade. Hence, this paper reviews the potential applications of TGases in textile and leather fabrication. The enzyme recovers the wool and silk damaged during chemical and enzymatic treatment at different stages of wool and silk processing. It enhances the shrink resistance of the wool and it improves the tensile strength of the wool fibers. In addition, TGase allows the grafting of amines or proteins to bring desired properties in wool fibers. Furthermore, smoothed and better color fastness can be obtained from wool treated with TGase. TGase is also used to fill voids with caseins and gelatines in leather industry. TGases play a great role in wool, silk and leather processing.
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