Skip to main content

Structure of Transglutaminases: Unique Features Serve Diverse Functions

  • Chapter
  • First Online:
Transglutaminases

Abstract

Understanding the diverse functions and pathologies of transglutaminases requires detailed analysis and interpretation of their structures. This chapter is an attempt to describe in detail how these enzymes are folded into functional domains, what type of catalytic and scaffolding functions have been gained as the result of their evolution, how their regulation is achieved through unique Ca2+ and purine nucleotide binding sites, redox changes and specific proteolytic actions, and by influencing the equilibrium of open-close configurations. The importance of structural motifs in pathologies is underlined by the celiac epitopes of transglutaminase 2, responsible for autoimmune reactions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Achyuthan KE, Greenberg CS (1987) Identification of a guanosine triphosphate-binding site on guinea pig liver transglutaminase. Role of GTP and calcium ions in modulating activity. J Biol Chem 262(4):1901–1906

    CAS  PubMed  Google Scholar 

  • Aeschlimann D, Paulsson M (1994) Transglutaminases: protein cross-linking enzymes in tissues and body fluids. Thromb Haemost 71(4):402–415

    CAS  PubMed  Google Scholar 

  • Agardh D, Dahlbom I et al (2005) Autoantibodies against soluble and immobilized human recombinant tissue transglutaminase in children with celiac disease. J Pediatr Gastroenterol Nutr 41(3):322–327

    Article  CAS  PubMed  Google Scholar 

  • Ahvazi B, Kim HC et al (2002) Three-dimensional structure of the human transglutaminase 3 enzyme: binding of calcium ions changes structure for activation. EMBO J 21(9):2055–2067

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ambrus A, Banyai I et al (2001) Calcium binding of transglutaminases: a 43Ca NMR study combined with surface polarity analysis. J Biomol Struct Dyn 19(1):59–74

    Article  CAS  PubMed  Google Scholar 

  • Anantharaman V, Aravind L (2003) Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes. Genome Biol 4(2):R11

    Article  PubMed Central  PubMed  Google Scholar 

  • Anantharaman V, Koonin EV et al (2001) Peptide-N-glycanases and DNA repair proteins, Xp-C/Rad4, are, respectively, active and inactivated enzymes sharing a common transglutaminase fold. Hum Mol Genet 10(16):1627–1630

    Article  CAS  PubMed  Google Scholar 

  • Ando Y, Imamura S et al (1989) Cross-linking of lipocortin I and enhancement of its Ca2+ sensitivity by tissue transglutaminase. Biochem Biophys Res Commun 163(2):944–951

    Article  CAS  PubMed  Google Scholar 

  • Azim AC, Marfatia SM et al (1996) Human erythrocyte dematin and protein 4.2 (pallidin) are ATP binding proteins. Biochemistry 35(9):3001–3006

    Article  CAS  PubMed  Google Scholar 

  • Baek KJ, Das T et al (1993) Evidence that the Gh protein is a signal mediator from α 1-adrenoceptor to a phospholipase C. I. Identification of α 1-adrenoceptor-coupled Gh family and purification of Gh7 from bovine heart. J Biol Chem 268:27390–27397

    CAS  PubMed  Google Scholar 

  • Baek KJ, Kwon NS et al (1996) Oxytocin receptor couples to the 80 kDa Gh α family protein in human myometrium. Biochem J 315:739–744

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Baker EN (1980) Structure of actinidin, after refinement at 1.7 A resolution. J Mol Biol 141(4):441–484

    Article  CAS  PubMed  Google Scholar 

  • Begg GE, Carrington L et al (2006) Mechanism of allosteric regulation of transglutaminase 2 by GTP. Proc Natl Acad Sci U S A 103(52):19683–19688

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Belkin AM, Zemskov EA et al (2004) Cell-surface-associated tissue transglutaminase is a target of MMP-2 proteolysis. Biochemistry 43(37):11760–11769

    Article  CAS  PubMed  Google Scholar 

  • Bergamini CM (1988) GTP modulates calcium binding and cation-induced conformational changes in erythrocyte transglutaminase. FEBS Lett 239(2):255–258

    Article  CAS  PubMed  Google Scholar 

  • Boeshans KM, Mueser TC et al (2007) A three-dimensional model of the human transglutaminase 1: insights into the understanding of lamellar ichthyosis. J Mol Model 13(1):233–246

    Article  CAS  PubMed  Google Scholar 

  • Boothe RL, Folk JE (1969) A reversible, calcium-dependent, copper-catalyzed inactivation of guinea pig liver transglutaminase. J Biol Chem 244(2):399–405

    CAS  PubMed  Google Scholar 

  • Boscolo S, Lorenzon A et al (2010) Anti transglutaminase antibodies cause ataxia in mice. PLoS One 5(3):e9698

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Candi E, Paradisi A et al (2004) Transglutaminase 5 is regulated by guanine-adenine nucleotides. Biochem J 381(Pt 1):313–319

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cardoso I, Stamnaes J et al (2015) Transglutaminase 2 interactions with extracellular matrix proteins as probed with celiac disease autoantibodies. FEBS J 282(11):2063–2075

    Article  CAS  PubMed  Google Scholar 

  • Cariello L, Ristoratore F et al (1997) A new transglutaminase-like from the ascidian Ciona intestinalis. FEBS Lett 408(2):171–176

    Article  CAS  PubMed  Google Scholar 

  • Caron NS, Munsie LN et al (2012) Using FLIM-FRET to measure conformational changes of transglutaminase type 2 in live cells. PLoS One 7(8):e44159

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chica RA, Gagnon P et al (2004) Tissue transglutaminase acylation: proposed role of conserved active site Tyr and Trp residues revealed by molecular modeling of peptide substrate binding. Protein Sci 13(4):979–991

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chung SI, Folk JE (1970) Mechanism of the inactivation of guinea pig liver transglutaminase by tetrathionate. J Biol Chem 245(4):681–689

    CAS  PubMed  Google Scholar 

  • Clouthier CM, Mironov GG et al (2012) Real-time monitoring of protein conformational dynamics in solution using kinetic capillary electrophoresis. Angew Chem Int Ed Engl 51(50):12464–12468

    Article  CAS  PubMed  Google Scholar 

  • Connellan JM, Folk JE (1969) Mechanism of the inactivation of guinea pig liver transglutaminase by 5,5′-dithiobis-(2-nitrobenzoic acid). J Biol Chem 244(12):3173–3181

    CAS  PubMed  Google Scholar 

  • Csosz E, Bagossi P et al (2008) Substrate preference of transglutaminase 2 revealed by logistic regression analysis and intrinsic disorder examination. J Mol Biol 383(2):390–402

    Article  CAS  PubMed  Google Scholar 

  • Csosz E, Mesko B et al (2009) Transdab wiki: the interactive transglutaminase substrate database on web 2.0 surface. Amino Acids 36(4):615–617

    Article  CAS  PubMed  Google Scholar 

  • Davey NE, Van Roey K et al (2012) Attributes of short linear motifs. Mol Biosyst 8(1):268–281

    Article  CAS  PubMed  Google Scholar 

  • Drenth J, Kalk KH et al (1976) Binding of chloromethyl ketone substrate analogues to crystalline papain. Biochemistry 15(17):3731–3738

    Article  CAS  PubMed  Google Scholar 

  • Feng JF, Gray CD et al (1999) Alpha 1B-adrenoceptor interacts with multiple sites of transglutaminase II: characteristics of the interaction in binding and activation. Biochemistry 38(7):2224–2232

    Article  CAS  PubMed  Google Scholar 

  • Folk JE (1969) Mechanism of action of guinea pig liver transglutaminase. VI. Order of substrate addition. J Biol Chem 244(13):3707–3713

    CAS  PubMed  Google Scholar 

  • Folk JE (1983) Mechanism and basis for specificity of transglutaminase-catalyzed epsilon-(gamma-glutamyl) lysine bond formation. Adv Enzymol Relat Areas Mol Biol 54:1–56

    CAS  PubMed  Google Scholar 

  • Folk JE, Cole PW (1965) Structural requirements of specific substrates for guinea pig liver transglutaminase. J Biol Chem 240:2951–2960

    CAS  PubMed  Google Scholar 

  • Folk JE, Cole PW (1966a) Identification of a functional cysteine essential for the activity of guinea pig liver transglutaminase. J Biol Chem 241(13):3238–3240

    CAS  PubMed  Google Scholar 

  • Folk JE, Cole PW (1966b) Mechanism of action of guinea pig liver transglutaminase. I. Purification and properties of the enzyme: identification of a functional cysteine essential for activity. J Biol Chem 241(23):5518–5525

    CAS  PubMed  Google Scholar 

  • Folk JE, Cole PW (1966c) Transglutaminase: mechanistic features of the active site as determined by kinetic and inhibitor studies. Biochim Biophys Acta 122(2):244–264

    Article  CAS  PubMed  Google Scholar 

  • Folk JE, Mullooly JP et al (1967) Mechanism of action of guinea pig liver transglutaminase. II. The role of metal in enzyme activation. J Biol Chem 242(8):1838–1844

    CAS  PubMed  Google Scholar 

  • Folk JE, Cole PW et al (1968) Mechanim of action of guinea pig liver transglutaminase. V. The hydrolysis reaction. J Biol Chem 243(2):418–427

    CAS  PubMed  Google Scholar 

  • Fox BA, Yee VC et al (1999) Identification of the calcium binding site and a novel ytterbium site in blood coagulation factor XIII by X-ray crystallography. J Biol Chem 274(8):4917–4923

    Article  CAS  PubMed  Google Scholar 

  • Fraij BM (1996) GTP hydrolysis by human tissue transglutaminase homologue. Biochem Biophys Res Commun 218(1):45–49

    Article  CAS  PubMed  Google Scholar 

  • Fuxreiter M, Tompa P, Simon I (2007) Local structural disorder imparts plasticity on linear motifs. Bioinformatics 23(8):950–956

    Article  CAS  PubMed  Google Scholar 

  • Gundersen MT, Keillor JW et al (2014) Microbial transglutaminase displays broad acyl-acceptor substrate specificity. Appl Microbiol Biotechnol 98(1):219–230

    Article  CAS  PubMed  Google Scholar 

  • Hadjivassiliou M, Aeschlimann P et al (2008) Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Ann Neurol 64(3):332–343

    Article  CAS  PubMed  Google Scholar 

  • Hadjivassiliou M, Aeschlimann P et al (2013) Transglutaminase 6 antibodies in the diagnosis of gluten ataxia. Neurology 80(19):1740–1745

    Article  CAS  PubMed  Google Scholar 

  • Han BG, Cho JW et al (2010) Crystal structure of human transglutaminase 2 in complex with adenosine triphosphate. Int J Biol Macromol 47(2):190–195

    Article  CAS  PubMed  Google Scholar 

  • Hang J, Zemskov EA et al (2005) Identification of a novel recognition sequence for fibronectin within the NH2-terminal beta-sandwich domain of tissue transglutaminase. J Biol Chem 280(25):23675–23683

    Article  CAS  PubMed  Google Scholar 

  • Hettasch JM, Greenberg CS (1994) Analysis of the catalytic activity of human factor XIIIa by site-directed mutagenesis. J Biol Chem 269(45):28309–28313

    CAS  PubMed  Google Scholar 

  • Husby S, Koletzko S et al (2012) European society for pediatric gastroenterology, hepatology, and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 54(1):136–160

    Article  CAS  PubMed  Google Scholar 

  • Hwang KC, Gray CD et al (1995) Interaction site of GTP binding Gh (transglutaminase II) with phospholipase C. J Biol Chem 270(45):27058–27062

    Article  CAS  PubMed  Google Scholar 

  • Iismaa SE, Chung L et al (1997) The core domain of the tissue transglutaminase Gh hydrolyzes GTP and ATP. Biochemistry 36(39):11655–11664

    Article  CAS  PubMed  Google Scholar 

  • Iismaa SE, Holman S et al (2003) Evolutionary specialization of a tryptophan indole group for transition-state stabilization by eukaryotic transglutaminases. Proc Natl Acad Sci U S A 100(22):12636–12641

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Im MJ, Riek RP et al (1990) A novel guanine nucleotide-binding protein coupled to the alpha 1-adrenergic receptor. II. Purification, characterization, and reconstitution. J Biol Chem 265(31):18952–18960

    CAS  PubMed  Google Scholar 

  • Iversen R, Di Niro R et al (2013) Transglutaminase 2-specific autoantibodies in celiac disease target clustered, N-terminal epitopes not displayed on the surface of cells. J Immunol 190(12):5981–5991

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Iversen R, Mysling S et al (2014) Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange. Proc Natl Acad Sci U S A 111(48):17146–17151

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jabs A, Weiss MS, Hilgenfeld R (1999) Non-proline cis peptide bonds in proteins. J Mol Biol 286(1):291–304

    Article  CAS  PubMed  Google Scholar 

  • Jang TH, Lee DS et al (2014) Crystal structure of transglutaminase 2 with GTP complex and amino acid sequence evidence of evolution of GTP binding site. PLoS One 9(9):e107005

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22(12):2577–2637

    Article  CAS  PubMed  Google Scholar 

  • Kanchan K, Ergulen E et al (2013) Identification of a specific one amino acid change in recombinant human transglutaminase 2 that regulates its activity and calcium sensitivity. Biochem J 455(3):261–272

    Article  CAS  PubMed  Google Scholar 

  • Kanchan K, Fuxreiter M, Fesus L (2015) Physiological, pathological and structural implications of non-enzymatic protein-protein interactions of the multifunctional human transglutaminase 2. Cell Mol Life Sci 72(16):3009–3035

    Article  CAS  PubMed  Google Scholar 

  • Kashiwagi T, Yokoyama K et al (2002) Crystal structure of microbial transglutaminase from Streptoverticillium mobaraense. J Biol Chem 277(46):44252–44260

    Article  CAS  PubMed  Google Scholar 

  • Keillor JW, Clouthier CM et al (2014) Acyl transfer mechanisms of tissue transglutaminase. Bioorg Chem 57:186–197

    Article  CAS  PubMed  Google Scholar 

  • Keillor JW, Apperley KY et al (2015) Inhibitors of tissue transglutaminase. Trends Pharmacol Sci 36(1):32–40

    Article  CAS  PubMed  Google Scholar 

  • Keresztessy Z, Csosz E et al (2006) Phage display selection of efficient glutamine-donor substrate peptides for transglutaminase 2. Protein Sci 15(11):2466–2480

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kim HC, Lewis MS et al (1990) Protransglutaminase E from guinea pig skin. Isolation and partial characterization. J Biol Chem 265(35):21971–21978

    CAS  PubMed  Google Scholar 

  • Kim IG, McBride OW et al (1992) Structure and organization of the human transglutaminase 1 gene. J Biol Chem 267(11):7710–7717

    CAS  PubMed  Google Scholar 

  • Kim SY, Kim IG et al (1994) The structure of the transglutaminase 1 enzyme. Deletion cloning reveals domains that regulate its specific activity and substrate specificity. J Biol Chem 269(45):27979–27986

    CAS  PubMed  Google Scholar 

  • Kiraly R, Csosz E et al (2009) Functional significance of five noncanonical Ca2+−binding sites of human transglutaminase 2 characterized by site-directed mutagenesis. FEBS J 276(23):7083–7096

    Article  CAS  PubMed  Google Scholar 

  • Kiraly R, Demeny M et al (2011) Protein transamidation by transglutaminase 2 in cells: a disputed Ca2 + −dependent action of a multifunctional protein. FEBS J 278(24):4717–4739

    Article  CAS  PubMed  Google Scholar 

  • Kiraly R, Tangaraju K et al (2015) Isopeptidase activity of human transglutaminase 2: disconnection from transamidation and characterization by kinetic parameters. Amino Acids [7 Aug 2015; Epub ahead of print]

    Google Scholar 

  • Korponay-Szabo IR, Sulkanen S et al (2000) Tissue transglutaminase is the target in both rodent and primate tissues for celiac disease-specific autoantibodies. J Pediatr Gastroenterol Nutr 31(5):520–527

    Article  CAS  PubMed  Google Scholar 

  • Korponay-Szabo IR, Halttunen T et al (2004) In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac autoantibodies. Gut 53(5):641–648

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Korponay-Szabo IR, Vecsei Z et al (2008) Deamidated gliadin peptides form epitopes that transglutaminase antibodies recognize. J Pediatr Gastroenterol Nutr 46(3):253–261

    Article  CAS  PubMed  Google Scholar 

  • Kuramoto K, Yamasaki R et al (2013) Phage-displayed peptide library screening for preferred human substrate peptide sequences for transglutaminase 7. Arch Biochem Biophys 537(1):138–143

    Article  CAS  PubMed  Google Scholar 

  • Ladinser B, Rossipal E et al (1994) Endomysium antibodies in coeliac disease: an improved method. Gut 35(6):776–778

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lai TS, Slaughter TF et al (1996) C-terminal deletion of human tissue transglutaminase enhances magnesium-dependent GTP/ATPase activity. J Biol Chem 271(49):31191–31195

    Article  CAS  PubMed  Google Scholar 

  • Lai TS, Liu Y et al (2007) Identification of two GTP-independent alternatively spliced forms of tissue transglutaminase in human leukocytes, vascular smooth muscle, and endothelial cells. FASEB J 21(14):4131–4143

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lewis BA, Freyssinet JM, Holbrook JJ (1978) An equilibrium study of metal ion binding to human plasma coagulation factor XIII. Biochem J 169(2):397–402

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lin YF, Yeh TS et al (2010) Nonmuscle myosin IIA (myosin heavy polypeptide 9): a novel class of signal transducer mediating the activation of G alpha h/phospholipase C-delta 1 pathway. Endocrinology 151(3):876–885

    Article  CAS  PubMed  Google Scholar 

  • Lindfors K, Koskinen O et al (2011) Serodiagnostic assays for celiac disease based on the open or closed conformation of the autoantigen, transglutaminase 2. J Clin Immunol 31(3):436–442

    Article  CAS  PubMed  Google Scholar 

  • Liu S, Cerione RA et al (2002) Structural basis for the guanine nucleotide-binding activity of tissue transglutaminase and its regulation of transamidation activity. Proc Natl Acad Sci U S A 99(5):2743–2747

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lorand L, Siefring GE Jr et al (1979) Dansylcadaverine specific staining for transamidating enzymes. Anal Biochem 93(2):453–458

    Article  CAS  PubMed  Google Scholar 

  • Lorand L, Dailey JE, Turner PM (1988) Fibronectin as a carrier for the transglutaminase from human erythrocytes. Proc Natl Acad Sci U S A 85(4):1057–1059

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lortat-Jacob H, Burhan I et al (2012) Transglutaminase-2 interaction with heparin: identification of a heparin binding site that regulates cell adhesion to fibronectin-transglutaminase-2 matrix. J Biol Chem 287(22):18005–18017

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Makarova KS, Aravind L et al (1999) A superfamily of archaeal, bacterial, and eukaryotic proteins homologous to animal transglutaminases. Protein Sci 8(8):1714–1719

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mariniello L, Esposito C et al (2003) N-terminus end of rat prostate transglutaminase is responsible for its catalytic activity and GTP binding. Int J Biochem Cell Biol 35(7):1098–1108

    Article  CAS  PubMed  Google Scholar 

  • Murthy SN, Lomasney JW et al (1999) Interactions of G(h)/transglutaminase with phospholipase Cdelta1 and with GTP. Proc Natl Acad Sci U S A 96(21):11815–11819

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Murthy SN, Iismaa S et al (2002) Conserved tryptophan in the core domain of transglutaminase is essential for catalytic activity. Proc Natl Acad Sci U S A 99(5):2738–2742

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Murzin AG, Brenner SE et al (1995) SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol 247(4):536–540

    CAS  PubMed  Google Scholar 

  • Muszbek L, Bereczky Z et al (2011) Factor XIII: a coagulation factor with multiple plasmatic and cellular functions. Physiol Rev 91(3):931–972

    Article  CAS  PubMed  Google Scholar 

  • Mycek MJ, Clarke DD et al (1959) Amine incorporation into insulin as catalyzed by transglutaminase. Arch Biochem Biophys 84(528):540

    Google Scholar 

  • Nakachi K, Powell M et al (2004) Epitopes recognised by tissue transglutaminase antibodies in coeliac disease. J Autoimmun 22(1):53–63

    Article  CAS  PubMed  Google Scholar 

  • Nakaoka H, Perez DM et al (1994) Gh: a GTP-binding protein with transglutaminase activity and receptor signaling function. Science 264(5165):1593–1596

    Article  CAS  PubMed  Google Scholar 

  • Nemes Z, Petrovski G et al (2005) Structure-function relationships of transglutaminases – a contemporary view. Prog Exp Tumor Res 38:19–36

    Article  CAS  PubMed  Google Scholar 

  • Nenna R, Tiberti C et al (2013) Anti-transglutaminase immunoreactivity and histological lesions of the duodenum in coeliac patients. Int Immunol 25(6):389–394

    Article  CAS  PubMed  Google Scholar 

  • Noguchi K, Ishikawa K et al (2001) Crystal structure of red sea bream transglutaminase. J Biol Chem 276(15):12055–12059

    Article  CAS  PubMed  Google Scholar 

  • Ohtsuka T, Ota M et al (2000) Comparison of substrate specificities of transglutaminases using synthetic peptides as acyl donors. Biosci Biotechnol Biochem 64(12):2608–2613

    Article  CAS  PubMed  Google Scholar 

  • Parameswaran KN, Cheng XF et al (1997) Hydrolysis of gamma: epsilon isopeptides by cytosolic transglutaminases and by coagulation factor XIIIa. J Biol Chem 272(15):10311–10317

    Article  CAS  PubMed  Google Scholar 

  • Pasternack R, Dorsch S et al (1998) Bacterial pro-transglutaminase from Streptoverticillium mobaraense – purification, characterisation and sequence of the zymogen. Eur J Biochem 257(3):570–576

    Article  CAS  PubMed  Google Scholar 

  • Pavlyukov MS, Antipova NV et al (2012) Detection of transglutaminase 2 conformational changes in living cell. Biochem Biophys Res Commun 421(4):773–779

    Article  CAS  PubMed  Google Scholar 

  • Pedersen LC, Yee VC et al (1994) Transglutaminase factor XIII uses proteinase-like catalytic triad to crosslink macromolecules. Protein Sci 3(7):1131–1135

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Peng X, Zhang Y et al (1999) Interaction of tissue transglutaminase with nuclear transport protein importin-alpha3. FEBS Lett 446(1):35–39

    Article  CAS  PubMed  Google Scholar 

  • Pietroni P, von Hippel PH (2008) Multiple ATP binding is required to stabilize the “activated” (clamp open) clamp loader of the T4 DNA replication complex. J Biol Chem 283(42):28338–28353

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pinkas DM, Strop P et al (2007) Transglutaminase 2 undergoes a large conformational change upon activation. PLoS Biol 5(12):e327

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Roth WJ, Chung SI et al (1986) Inactivation of alveolar macrophage transglutaminase by oxidants in cigarette smoke. J Leukoc Biol 39(6):629–644

    CAS  PubMed  Google Scholar 

  • Sardy M, Karpati S et al (2002) Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis. J Exp Med 195(6):747–757

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sblattero D, Florian F et al (2002) The analysis of the fine specificity of celiac disease antibodies using tissue transglutaminase fragments. Eur J Biochem 269(21):5175–5181

    Article  CAS  PubMed  Google Scholar 

  • Seissler J, Wohlrab U et al (2001) Autoantibodies from patients with coeliac disease recognize distinct functional domains of the autoantigen tissue transglutaminase. Clin Exp Immunol 125(2):216–221

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Siegel M, Strnad P et al (2008) Extracellular transglutaminase 2 is catalytically inactive, but is transiently activated upon tissue injury. PLoS One 3(3):e1861

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Simon-Vecsei Z, Kiraly R et al (2012) A single conformational transglutaminase 2 epitope contributed by three domains is critical for celiac antibody binding and effects. Proc Natl Acad Sci U S A 109(2):431–436

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stamnaes J, Pinkas DM et al (2010) Redox regulation of transglutaminase 2 activity. J Biol Chem 285(33):25402–25409

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Steinert PM, Chung SI et al (1996a) Inactive zymogen and highly active proteolytically processed membrane-bound forms of the transglutaminase 1 enzyme in human epidermal keratinocytes. Biochem Biophys Res Commun 221(1):101–106

    Article  CAS  PubMed  Google Scholar 

  • Steinert PM, Kim SY et al (1996b) The transglutaminase 1 enzyme is variably acylated by myristate and palmitate during differentiation in epidermal keratinocytes. J Biol Chem 271(42):26242–26250

    Article  CAS  PubMed  Google Scholar 

  • Stenberg R, Hadjivassiliou M et al (2014) Anti-transglutaminase 6 antibodies in children and young adults with cerebral palsy. Autoimmun Dis 2014:237107

    Google Scholar 

  • Stieler M, Weber J et al (2013) Structure of active coagulation factor XIII triggered by calcium binding: basis for the design of next-generation anticoagulants. Angew Chem Int Ed Engl 52(45):11930–11934

    Article  CAS  PubMed  Google Scholar 

  • Sugimura Y, Hosono M et al (2006) Screening for the preferred substrate sequence of transglutaminase using a phage-displayed peptide library: identification of peptide substrates for TGASE 2 and Factor XIIIA. J Biol Chem 281(26):17699–17706

    Article  CAS  PubMed  Google Scholar 

  • Sugimura Y, Hosono M et al (2008) Identification of preferred substrate sequences for transglutaminase 1 – development of a novel peptide that can efficiently detect cross-linking enzyme activity in the skin. FEBS J 275(22):5667–5677

    Article  CAS  PubMed  Google Scholar 

  • Tanfani F, Bertoli E et al (1993) Structural investigation of transglutaminase by Fourier transform infrared spectroscopy. Eur J Biochem 218(2):499–505

    Article  CAS  PubMed  Google Scholar 

  • Teesalu K, Panarina M et al (2012) Autoantibodies from patients with celiac disease inhibit transglutaminase 2 binding to heparin/heparan sulfate and interfere with intestinal epithelial cell adhesion. Amino Acids 42(2–3):1055–1064

    Article  CAS  PubMed  Google Scholar 

  • Thomas H, Beck K et al (2013) Transglutaminase 6: a protein associated with central nervous system development and motor function. Amino Acids 44(1):161–177

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tiberti C, Bao F et al (2003) Celiac disease-associated transglutaminase autoantibody target domains at diagnosis are age and sex dependent. Clin Immunol 109(3):318–324

    Article  CAS  PubMed  Google Scholar 

  • Tokunaga F, Muta T et al (1993) Limulus hemocyte transglutaminase. cDNA cloning, amino acid sequence, and tissue localization. J Biol Chem 268(1):262–268

    CAS  PubMed  Google Scholar 

  • Tyagi S, VanDelinder V et al (2014) Continuous throughput and long-term observation of single-molecule FRET without immobilization. Nat Methods 11(3):297–300

    Article  CAS  PubMed  Google Scholar 

  • Vezza R, Habib A, FitzGerald GA (1999) Differential signaling by the thromboxane receptor isoforms via the novel GTP-binding protein, Gh. J Biol Chem 274:12774–12779

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Collighan RJ et al (2012) Characterization of heparin-binding site of tissue transglutaminase: its importance in cell surface targeting, matrix deposition, and cell signaling. J Biol Chem 287(16):13063–13083

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ward JJ, Sodhi JS et al (2004) Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. J Mol Biol 337(3):635–645

    Article  CAS  PubMed  Google Scholar 

  • Weiss MS, Metzner HJ et al (1998) Two non-proline cis peptide bonds may be important for factor XIII function. FEBS Lett 423(3):291–296

    Article  CAS  PubMed  Google Scholar 

  • Weraarchakul-Boonmark N, Jeong JM et al (1992) Cloning and expression of chicken erythrocyte transglutaminase. Proc Natl Acad Sci U S A 89(20):9804–9808

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yamane A, Fukui M et al (2010) Identification of a preferred substrate peptide for transglutaminase 3 and detection of in situ activity in skin and hair follicles. FEBS J 277(17):3564–3574

    Article  CAS  PubMed  Google Scholar 

  • Yee VC, Pedersen LC et al (1994) Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII. Proc Natl Acad Sci U S A 91(15):7296–7300

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yee VC, Pedersen LC et al (1995) Structural evidence that the activation peptide is not released upon thrombin cleavage of factor XIII. Thromb Res 78(5):389–397

    Article  CAS  PubMed  Google Scholar 

  • Zemskov EA, Mikhailenko I et al (2011) Unconventional secretion of tissue transglutaminase involves phospholipid-dependent delivery into recycling endosomes. PLoS One 6(4):e19414

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhang D, Aravind L (2012) Novel transglutaminase-like peptidase and C2 domains elucidate the structure, biogenesis and evolution of the ciliary compartment. Cell Cycle 11(20):3861–3875

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to László Fésüs .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this chapter

Cite this chapter

Demény, M.Á., Korponay-Szabó, I., Fésüs, L. (2015). Structure of Transglutaminases: Unique Features Serve Diverse Functions. In: Hitomi, K., Kojima, S., Fesus, L. (eds) Transglutaminases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55825-5_1

Download citation

Publish with us

Policies and ethics