Article

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

ABSTRACT

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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    • "tTGase is a calcium dependent enzyme, ubiquitously expressed, that plays a vast array of biological functions. It is considered the " auto-antigen " of CD as gluten intake induces secretion of IgA-class autoantibodies that target tTGase [5]. Another class of autoantibodies, described in 90.3% paediatric and 59.6% adult patients with active CD and very damaged mucosa, is the antifilamentous actin antibodies (A-FAA) which has therefore been considered by some authors an additional CD diagnostic tool [6] [7]. "
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    ABSTRACT: Celiac disease (CD) is the most common autoimmune enteropathy. Clinical manifestations may range from a typical malabsorption syndrome to several apparently unrelated extra-intestinal symptoms.
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    • "Ruminant animals have generally adapted to these potentially offensive plant chemicals through the evolution of their four fermentation stomachs which aid adequate gastric enzymatic splitting of proteins and digestive deactivation of peptides before they enter the intestines. Transglutaminase is a naturallyoccurring enzyme in the rumen which deamidates gliadin and catalyses glutenin into glutamine and glutamates (Griffin et al, 2002). There is little or no auto-immune antibody response to offending plant chemicals in ruminant animals because of this deamidation and catalysis. "
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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.
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