Skip to main content
SpringerLink
Log in

Structure of Shiga Toxins and Other AB5 Toxins

  • Chapter
  • First Online:
Shiga toxins

Part of the book series: Food Microbiology and Food Safety ((RESDEV))

Abstract

Shiga toxins (Stx) are part of a general class of protein toxins referred to as AB5 holotoxins, including pertussis toxin, cholera toxin, E. coli heat-labile enterotoxins, and subtilase cytotoxin. The structural differences between the types and subtypes of Shiga toxins subtly influence the specificity and strength of binding of these toxins. There are two types of Shiga toxins, Stx1 and Stx2, each of which has multiple genetic variants. Each Shiga toxin has five identical B subunits that bind to gangliosides, such as the globotriaosylceramide (Gb3) on the surface of the target eukaryotic cell. The B subunits of Stx1 and Stx2 differ substantially from each other (62% identical), but within each of the Stx1 or Sxt2 types, the B subunits are more than 80% identical. The A subunits of Stx1 and Stx2 have the same enzymatic activity, but are less than 60% identical. The A1 domain of the A subunit is released by an intracellular protease, and its specific N-glycosidase can then inactivate the 60S subunit of ribosomes. A single holotoxin molecule that is properly delivered and processed is sufficient to kill a target cell by inhibiting protein synthesis.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

References

  • Antoine R, Locht C (1990) Roles of the disulfide bond and the carboxy-terminal region of the S1 subunit in the assembly and biosynthesis of pertussis toxin. Infect Immun 58(6):1518–1526

    CAS  PubMed  PubMed Central  Google Scholar 

  • Arab S, Lingwood CA (1996) Influence of phospholipid chain length on verotoxin/globotriaosyl ceramide binding in model membranes: comparison of a supported bilayer film and liposomes. Glycoconj J 13(2):159–166

    Article  CAS  PubMed  Google Scholar 

  • Armstrong GD, Mulvey GL, Marcato P, Griener TP, Kahan MC, Tennent GA, Sabin CA, Chart H, Pepys MB (2006) Human serum amyloid P component protects against Escherichia coli O157:H7 Shiga toxin 2 in vivo: therapeutic implications for hemolytic-uremic syndrome. J Infect Dis 193(8):1120–1124

    Article  PubMed  Google Scholar 

  • Ashkenazi S, Cleary TG, Lopez E, Pickering LK (1988) Anticytotoxin-neutralizing antibodies in immune globulin preparations: potential use in hemolytic-uremic syndrome. J Pediatr 113(6):1008–1014

    Article  CAS  PubMed  Google Scholar 

  • Basu D, Li XP, Kahn JN, May KL, Kahn PC, Tumer NE (2016) The A1 subunit of Shiga toxin 2 has higher affinity for ribosomes and higher catalytic activity than the A1 subunit of Shiga toxin 1. Infect Immun 84(1):149–161

    Article  CAS  Google Scholar 

  • Beutin L, Strauch E, Fischer I (1999) Isolation of Shigella sonnei lysogenic for a bacteriophage encoding gene for production of Shiga toxin. Lancet 353(9163):1498

    Article  CAS  PubMed  Google Scholar 

  • Binnington B, Lingwood D, Nutikka A, Lingwood CA (2002) Effect of globotriaosyl ceramide fatty acid alpha-hydroxylation on the binding by verotoxin 1 and verotoxin 2. Neurochem Res 27(7–8):807–813

    Article  CAS  PubMed  Google Scholar 

  • Bitzan M, Klemt M, Steffens R, Muller-Wiefel DE (1993a) Differences in verotoxin neutralizing activity of therapeutic immunoglobulins and sera from healthy controls. Infection 21(3):140–145

    Article  CAS  PubMed  Google Scholar 

  • Bitzan M, Ludwig K, Klemt M, Konig H, Buren J, Muller-Wiefel DE (1993b) The role of Escherichia coli O 157 infections in the classical (enteropathic) haemolytic uraemic syndrome: results of a Central European, multicentre study. Epidemiol Infect 110(2):183–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boerlin P, McEwen SA, Boerlin-Petzold F, Wilson JB, Johnson RP, Gyles CL (1999) Associations between virulence factors of Shiga toxin-producing Escherichia coli and disease in humans. J Clin Microbiol 37(3):497–503

    CAS  PubMed  PubMed Central  Google Scholar 

  • Breimer ME, Hansson GC, Karlsson KA, Leffler H (1982) Studies on differentiating epithelial cells of rat small intestine. Alterations in the lipophilic part of glycosphingolipids during cell migration from crypt villus tip. Biochim Biophys Acta 710(3):415–427

    Article  CAS  PubMed  Google Scholar 

  • Brown CA, Harmon BG, Zhao T, Doyle MP (1997) Experimental Escherichia coli O157:H7 carriage in calves. Appl Environ Microbiol 63(1):27–32

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bunger JC, Melton-Celsa AR, Maynard EL, O’Brien AD (2015) Reduced toxicity of Shiga toxin (Stx) type 2c in mice compared to Stx2d is associated with instability of Stx2c holotoxin. Toxins (Basel) 7(6):2306–2320

    Article  CAS  Google Scholar 

  • Byres E, Paton AW, Paton JC, Lofling JC, Smith DF, Wilce MC, Talbot UM, Chong DC, Yu H, Huang S, Chen X, Varki NM, Varki A, Rossjohn J, Beddoe T (2008) Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin. Nature 456(7222):648–652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calderwood SB, Mekalanos JJ (1987) Iron regulation of Shiga-like toxin expression in Escherichia coli is mediated by the fur locus. J Bacteriol 169(10):4759–4764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calderwood SB, Auclair F, Donohue-Rolfe A, Keusch GT, Mekalanos JJ (1987) Nucleotide sequence of the Shiga-like toxin genes of Escherichia coli. Proc Natl Acad Sci U S A 84(13):4364–4368

    Article  PubMed  PubMed Central  Google Scholar 

  • Cao C, Kurazono H, Yamasaki S, Kashiwagi K, Igarashi K, Takeda Y (1994) Construction of mutant genes for a non-toxic verotoxin 2 variant (VT2vp1) of Escherichia coli and characterization of purified mutant toxins. Microbiol Immunol 38(6):441–447

    Article  CAS  PubMed  Google Scholar 

  • Caprioli A, Luzzi I, Rosmini F, Pasquini P, Cirrincione R, Gianviti A, Matteucci MC, Rizzoni G (1992) Hemolytic-uremic syndrome and Vero cytotoxin-producing Escherichia coli infection in Italy. The HUS Italian Study Group. J Infect Dis 166(1):154–158

    Article  CAS  PubMed  Google Scholar 

  • Caprioli A, Luzzi I, Seganti L, Marchetti M, Karmali MA, Clarke I, Boyd B (1994) Frequency and nature of verocytotoxin 2 (VT2) neutralizing activity (NA) in human and animal sera. In: Karmali MA, Goglio A (eds) Recent advances in verocytotoxin-producing Escherichia coli infections. Elsevier, Amsterdam, pp 353–356

    Google Scholar 

  • Cassel D, Pfeuffer T (1978) Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. Proc Natl Acad Sci U S A 75(6):2669–2673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cassel D, Selinger Z (1977) Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. Proc Natl Acad Sci U S A 74(8):3307–3311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chark D, Nutikka A, Trusevych N, Kuzmina J, Lingwood C (2004) Differential carbohydrate epitope recognition of globotriaosyl ceramide by verotoxins and a monoclonal antibody. Eur J Biochem 271(2):405–417

    Article  CAS  PubMed  Google Scholar 

  • Conrady DG, Flagler MJ, Friedmann DR, Vander Wielen BD, Kovall RA, Weiss AA, Herr AB (2010) Molecular basis of differential B-pentamer stability of Shiga toxins 1 and 2. PLoS One 5(12):e15153. doi:10.1371/journal.pone.0015153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox N, Pilling D, Gomer RH (2014) Serum amyloid P: a systemic regulator of the innate immune response. J Leukoc Biol 96(5):739–743

    Article  PubMed  CAS  Google Scholar 

  • Cray WC Jr, Moon HW (1995) Experimental infection of calves and adult cattle with Escherichia coli O157:H7. Appl Environ Microbiol 61(4):1586–1590

    CAS  PubMed  PubMed Central  Google Scholar 

  • DeGrandis S, Ginsberg J, Toone M, Climie S, Friesen J, Brunton J (1987) Nucleotide sequence and promoter mapping of the Escherichia coli Shiga-like toxin operon of bacteriophage H-19B. J Bacteriol 169(9):4313–4319

    Article  CAS  Google Scholar 

  • DeGrandis S, Law H, Brunton J, Gyles C, Lingwood CA (1989) Globotetraosylceramide is recognized by the pig edema disease toxin. J Biol Chem 264(21):12520–12525

    CAS  PubMed  Google Scholar 

  • Deresiewicz RL, Calderwood SB, Robertus JD, Collier RJ (1992) Mutations affecting the activity of the Shiga-like toxin I A-chain. Biochemistry 31(12):3272–3280

    Article  CAS  PubMed  Google Scholar 

  • Deresiewicz RL, Austin PR, Hovde CJ (1993) The role of tyrosine-114 in the enzymatic activity of the Shiga-like toxin I A-chain. Mol Gen Genet 241(3–4):467–473

    CAS  PubMed  Google Scholar 

  • Di R, Kyu E, Shete V, Saidasan H, Kahn PC, Tumer NE (2011) Identification of amino acids critical for the cytotoxicity of Shiga toxin 1 and 2 in Saccharomyces cerevisiae. Toxicon 57(4):525–539

    Article  CAS  PubMed  Google Scholar 

  • Emsley J, White HE, O’Hara BP, Oliva G, Srinivasan N, Tickle IJ, Blundell TL, Pepys MB, Wood SP (1994) Structure of pentameric human serum amyloid P component. Nature 367(6461):338–345

    Article  CAS  PubMed  Google Scholar 

  • Endo Y, Tsurugi K, Yutsudo T, Takeda Y, Ogasawara T, Igarashi K (1988) Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and of Shiga toxin on eukaryotic ribosomes. RNA N-glycosidase activity of the toxins. Eur J Biochem 171(1–2):45–50

    Article  CAS  PubMed  Google Scholar 

  • Engedal N, Skotland T, Torgersen ML, Sandvig K (2011) Shiga toxin and its use in targeted cancer therapy and imaging. J Microbial Biotechnol 4(1):32–46

    Article  CAS  Google Scholar 

  • Falguieres T, Mallard F, Baron C, Hanau D, Lingwood C, Goud B, Salamero J, Johannes L (2001) Targeting of Shiga toxin B-subunit to retrograde transport route in association with detergent-resistant membranes. Mol Biol Cell 12(8):2453–2468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan E, Merritt EA, Verlinde CL, Hol WG (2000) AB(5) toxins: structures and inhibitor design. Curr Opin Struct Biol 10(6):680–686

    Article  CAS  PubMed  Google Scholar 

  • Flagler MJ, Mahajan SS, Kulkarni AA, Iyer SS, Weiss AA (2010) Comparison of binding platforms yields insights into receptor binding differences between Shiga toxins 1 and 2. Biochemistry 49(8):1649–1657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fraser ME, Chernaia MM, Kozlov YV, James MN (1994) Crystal structure of the holotoxin from Shigella dysenteriae at 2.5 A resolution. Nat Struct Biol 1(1):59–64

    Article  CAS  PubMed  Google Scholar 

  • Fraser ME, Fujinaga M, Cherney MM, Melton-Celsa AR, Twiddy EM, O’Brien AD, James MN (2004) Structure of Shiga toxin type 2 (Stx2) from Escherichia coli O157:H7. J Biol Chem 279(26):27511–27517

    Article  CAS  PubMed  Google Scholar 

  • Fuller CA, Pellino CA, Flagler MJ, Strasser JE, Weiss AA (2011) Shiga toxin subtypes display dramatic differences in potency. Infect Immun 79(3):1329–1337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gallegos KM, Conrady DG, Karve SS, Gunasekera TS, Herr AB, Weiss AA (2012) Shiga toxin binding to glycolipids and glycans. PLoS One 7(2):e30368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garred O, Dubinina E, Holm PK, Olsnes S, van Deurs B, Kozlov JV, Sandvig K (1995a) Role of processing and intracellular transport for optimal toxicity of Shiga toxin and toxin mutants. Exp Cell Res 218(1):39–49

    Article  CAS  PubMed  Google Scholar 

  • Garred O, van Deurs B, Sandvig K (1995b) Furin-induced cleavage and activation of Shiga toxin. J Biol Chem 270(18):10817–10821

    Article  CAS  PubMed  Google Scholar 

  • Garred O, Dubinina E, Polesskaya A, Olsnes S, Kozlov J, Sandvig K (1997) Role of the disulfide bond in Shiga toxin A-chain for toxin entry into cells. J Biol Chem 272(17):11414–11419

    Article  CAS  PubMed  Google Scholar 

  • Gill DM, Meren R (1978) ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. Proc Natl Acad Sci U S A 75(7):3050–3054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gray MD, Lampel KA, Strockbine NA, Fernandez RE, Melton-Celsa AR, Maurelli AT (2014) Clinical isolates of Shiga toxin 1a-producing Shigella flexneri with an epidemiological link to recent travel to Hispaniola. Emerg Infect Dis 20(10):1669–1677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gross R, Rappuoli R (1988) Positive regulation of pertussis toxin expression. Proc Natl Acad Sci U S A 85(11):3913–3917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Habib NF, Jackson MP (1992) Identification of a B subunit gene promoter in the Shiga toxin operon of Shigella dysenteriae 1. J Bacteriol 174(20):6498–6507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Habib NF, Jackson MP (1993) Roles of a ribosome-binding site and mRNA secondary structure in differential expression of Shiga toxin genes. J Bacteriol 175(3):597–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hazes B, Boodhoo A, Cockle SA, Read RJ (1996) Crystal structure of the pertussis toxin-ATP complex: a molecular sensor. J Mol Biol 258(4):661–671

    Article  CAS  PubMed  Google Scholar 

  • Head SC, Karmali MA, Lingwood CA (1991) Preparation of VT1 and VT2 hybrid toxins from their purified dissociated subunits. Evidence for B subunit modulation of a subunit function. J Biol Chem 266(6):3617–3621

    CAS  PubMed  Google Scholar 

  • Hehnly H, Sheff D, Stamnes M (2006) Shiga toxin facilitates its retrograde transport by modifying microtubule dynamics. Mol Biol Cell 17(10):4379–4389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoey DE, Sharp L, Currie C, Lingwood CA, Gally DL, Smith DG (2003) Verotoxin 1 binding to intestinal crypt epithelial cells results in localization to lysosomes and abrogation of toxicity. Cell Microbiol 5(2):85–97

    Article  CAS  PubMed  Google Scholar 

  • Hovde CJ, Calderwood SB, Mekalanos JJ, Collier RJ (1988) Evidence that glutamic acid 167 is an active-site residue of Shiga-like toxin I. Proc Natl Acad Sci U S A 85(8):2568–2572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang A, Friesen J, Brunton JL (1987) Characterization of a bacteriophage that carries the genes for production of Shiga-like toxin 1 in Escherichia coli. J Bacteriol 169(9):4308–4312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hussein HS, Bollinger LM (2005) Prevalence of Shiga toxin-producing Escherichia coli in beef cattle. J Food Prot 68(10):2224–2241

    Article  PubMed  Google Scholar 

  • Igarashi K, Ogasawara T, Ito K, Yutsudo T, Takeda Y (1987) Inhibition of elongation factor 1-dependent aminoacyltRNA binding to ribosomes by Shiga-like toxin I (VT1) from Escherichia coli 0157:H7 and by Shiga toxin. FEMS Microbiol Lett 44:91–94

    Article  CAS  Google Scholar 

  • Ito H, Yutsudo T, Hirayama T, Takeda Y (1988) Isolation and some properties of A and B subunits of Vero toxin 2 and in vitro formation of hybrid toxins between subunits of Vero toxin 1 and Vero toxin 2 from Escherichia coli O157:H7. Microb Pathog 5(3):189–195

    Article  CAS  PubMed  Google Scholar 

  • Itoh K, Tezuka T, Inoue K, Tada H, Suzuki T (2001) Different binding property of verotoxin-1 and verotoxin-2 against their glycolipid receptor, globotriaosylceramide. Tohoku J Exp Med 195(4):237–243

    Article  CAS  PubMed  Google Scholar 

  • Jacewicz M, Clausen H, Nudelman E, Donohue-Rolfe A, Keusch GT (1986) Pathogenesis of Shigella diarrhea XI isolation of a Shigella toxin-binding glycolipid from rabbit jejunum and HeLa cells and its identification as globotriaosylceramide. J Exp Med 163(6):1391–1404

    Article  CAS  PubMed  Google Scholar 

  • Jackson MP, Deresiewicz RL, Calderwood SB (1990) Mutational analysis of the Shiga toxin and Shiga-like toxin II enzymatic subunits. J Bacteriol 172(6):3346–3350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobson JM, Yin J, Kitov PI, Mulvey G, Griener TP, James MN, Armstrong G, Bundle DR (2014) The crystal structure of Shiga toxin type 2 with bound disaccharide guides the design of a heterobifunctional toxin inhibitor. J Biol Chem 289(2):885–894

    Article  CAS  PubMed  Google Scholar 

  • Jemal C, Haddad JE, Begum D, Jackson MP (1995) Analysis of Shiga toxin subunit association by using hybrid A polypeptides and site-specific mutagenesis. J Bacteriol 177(11):3128–3132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Katagiri YU, Mori T, Nakajima H, Katagiri C, Taguchi T, Takeda T, Kiyokawa N, Fujimoto J (1999) Activation of Src family kinase yes induced by Shiga toxin binding to globotriaosyl ceramide (Gb3/CD77) in low density, detergent-insoluble microdomains. J Biol Chem 274(49):35278–35282

    Article  CAS  PubMed  Google Scholar 

  • Keusch GT, Jacewicz M, Donohue-Rolfe A (1986) Pathogenesis of Shigella diarrhea: evidence for an N-linked glycoprotein Shigella toxin receptor and receptor modulation by beta-galactosidase. J Infect Dis 153(2):238–248

    Article  CAS  PubMed  Google Scholar 

  • Kiarash A, Boyd B, Lingwood CA (1994) Glycosphingolipid receptor function is modified by fatty acid content. Verotoxin 1 and verotoxin 2c preferentially recognize different globotriaosyl ceramide fatty acid homologues. J Biol Chem 269(15):11138–11146

    CAS  PubMed  Google Scholar 

  • Kimura T, Tani S, Matsumoto Yi Y, Takeda T (2001) Serum amyloid P component is the Shiga toxin 2-neutralizing factor in human blood. J Biol Chem 276(45):41576–41579

    Article  CAS  PubMed  Google Scholar 

  • Kimura T, Tani S, Motoki M, Matsumoto Y (2003) Role of Shiga toxin 2 (Stx2)-binding protein, human serum amyloid P component (HuSAP), in Shiga toxin-producing Escherichia coli infections: assumption from in vitro and in vivo study using HuSAP and anti-Stx2 humanized monoclonal antibody TMA-15. Biochem Biophys Res Commun 305(4):1057–1060

    Article  CAS  PubMed  Google Scholar 

  • Kitova EN, Daneshfar R, Marcato P, Mulvey GL, Armstrong G, Klassen JS (2005) Stability of the homopentameric B subunits of Shiga toxins 1 and 2 in solution and the gas phase as revealed by nanoelectrospray Fourier transform ion cyclotron resonance mass spectrometry. J Am Soc Mass Spectrom 16(12):1957–1968

    Article  CAS  PubMed  Google Scholar 

  • Kitova EN, Mulvey GL, Dingle T, Sinelnikov I, Wee S, Griener TP, Armstrong GD, Klassen JS (2009) Assembly and stability of the Shiga toxins investigated by electrospray ionization mass spectrometry. Biochemistry 48(23):5365–5374

    Article  CAS  PubMed  Google Scholar 

  • Kongmuang U, Honda T, Miwatani T (1988) Effect of nicking on Shiga-like toxin I of enterohaemorrhagic Escherichia coli. FEMS Microbiol Lett 56:105–108

    Article  CAS  Google Scholar 

  • Konowalchuk J, Speirs JI, Stavric S (1977) Vero response to a cytotoxin of Escherichia coli. Infect Immun 18(3):775–779

    CAS  PubMed  PubMed Central  Google Scholar 

  • Konowalchuk J, Dickie N, Stavric S, Speirs JI (1978) Properties of an Escherichia coli cytotoxin. Infect Immun 20(2):575–577

    CAS  PubMed  PubMed Central  Google Scholar 

  • LaPointe P, Wei X, Gariepy J (2005) A role for the protease-sensitive loop region of Shiga-like toxin 1 in the retrotranslocation of its A1 domain from the endoplasmic reticulum lumen. J Biol Chem 280(24):23310–23318

    Article  CAS  PubMed  Google Scholar 

  • Lauvrak SU, Walchli S, Iversen TG, Slagsvold HH, Torgersen ML, Spilsberg B, Sandvig K (2006) Shiga toxin regulates its entry in a Syk-dependent manner. Mol Biol Cell 17(3):1096–1109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Le Nours J, Paton AW, Byres E, Troy S, Herdman BP, Johnson MD, Paton JC, Rossjohn J, Beddoe T (2013) Structural basis of subtilase cytotoxin SubAB assembly. J Biol Chem 288(38):27505–27516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levental I, Veatch SL (2016) The continuing mystery of lipid rafts. 428(24 Pt A):4749–4764. http://ac.els-cdn.com/S0022283616303412/0022283616303411-s0022283616303412.0022283616303410-S0022283616303412-main.pdf?_tid=0022283616389182c0022283616303428-0022283616303416fa0022283616303413-0022283616303411e0022283616303416-0022283616303419d0022283616303480-0022283616300000aacb0022283616303435f&acdnat=0022281472666065_0022283616303406d0022283616303414ede0022283616303410a0022283616303410daf0022283616303434c0022283616397258b0022283616303416eb0022283616306375dd0022283616303410

  • Lindberg AA, Brown JE, Stromberg N, Westling-Ryd M, Schultz JE, Karlsson KA (1987) Identification of the carbohydrate receptor for Shiga toxin produced by Shigella dysenteriae type 1. J Biol Chem 262(4):1779–1785

    CAS  PubMed  Google Scholar 

  • Ling H, Boodhoo A, Hazes B, Cummings MD, Armstrong GD, Brunton JL, Read RJ (1998) Structure of the Shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3. Biochemistry 37(7):1777–1788

    Article  CAS  PubMed  Google Scholar 

  • Lingwood CA, Law H, Richardson S, Petric M, Brunton JL, De Grandis S, Karmali M (1987) Glycolipid binding of purified and recombinant Escherichia coli produced verotoxin in vitro. J Biol Chem 262(18):8834–8839

    CAS  PubMed  Google Scholar 

  • MacLeod DL, Gyles CL, Valdivieso-Garcia A, Clarke RC (1991) Physicochemical and biological properties of purified Escherichia coli Shiga-like toxin II variant. Infect Immun 59(4):1300–1306

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mahfoud R, Manis A, Lingwood CA (2009) Fatty acid-dependent globotriaosyl ceramide receptor function in detergent resistant model membranes. J Lipid Res 50(9):1744–1755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marcato P, Vander Helm K, Mulvey GL, Armstrong GD (2003) Serum amyloid P component binding to Shiga toxin 2 requires both a subunit and B pentamer. Infect Immun 71(10):6075–6078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McDonough MA, Butterton JR (1999) Spontaneous tandem amplification and deletion of the Shiga toxin operon in Shigella dysenteriae 1. Mol Microbiol 34(5):1058–1069

    Article  CAS  PubMed  Google Scholar 

  • Mizutani S, Nakazono N, Sugino Y (1999) The so-called chromosomal verotoxin genes are actually carried by defective prophages. DNA Res 6(2):141–143

    Article  CAS  PubMed  Google Scholar 

  • Mori T, Kiyokawa N, Katagiri YU, Taguchi T, Suzuki T, Sekino T, Sato N, Ohmi K, Nakajima H, Takeda T, Fujimoto J (2000) Globotriaosyl ceramide (CD77/Gb3) in the glycolipid-enriched membrane domain participates in B-cell receptor-mediated apoptosis by regulating lyn kinase activity in human B cells. Exp Hematol 28(11):1260–1268

    Article  CAS  PubMed  Google Scholar 

  • Morooka T, Umeda A, Winkler M, Karmali MA, Amako K, Oda T (1996) Anti-verocytotoxin (VT)1, VT2 and VT2c antibodies in commercial intravenous immune globulins in Japan. Acta Paediatr Jpn 38(3):294–295

    Article  CAS  PubMed  Google Scholar 

  • Nakajima H, Kiyokawa N, Katagiri YU, Taguchi T, Suzuki T, Sekino T, Mimori K, Ebata T, Saito M, Nakao H, Takeda T, Fujimoto J (2001) Kinetic analysis of binding between Shiga toxin and receptor glycolipid Gb3Cer by surface plasmon resonance. J Biol Chem 276(46):42915–42922

    Article  CAS  PubMed  Google Scholar 

  • Nataro JP, Kaper JB (1998) Diarrheagenic Escherichia coli. Clin Microbiol Rev 11(1):142–201

    CAS  PubMed  PubMed Central  Google Scholar 

  • Newland JW, Strockbine NA, Miller SF, O’Brien AD, Holmes RK (1985) Cloning of Shiga-like toxin structural genes from a toxin converting phage of Escherichia coli. Science 230(4722):179–181

    Article  CAS  PubMed  Google Scholar 

  • O’Brien AD, Newland JW, Miller SF, Holmes RK, Smith HW, Formal SB (1984) Shiga-like toxin-converting phages from Escherichia coli strains that cause hemorrhagic colitis or infantile diarrhea. Science 226(4675):694–696

    Article  PubMed  Google Scholar 

  • O’Keefe E, Cuatecasas P (1978) Cholera toxin and membrane gangliosides: binding and adenylate cyclase activation in normal and transformed cells. J Membr Biol 42(1):61–79

    Article  PubMed  Google Scholar 

  • O’Neal CJ, Amaya EI, Jobling MG, Holmes RK, Hol WG (2004) Crystal structures of an intrinsically active cholera toxin mutant yield insight into the toxin activation mechanism. Biochemistry 43(13):3772–3782

    Article  PubMed  CAS  Google Scholar 

  • O’Neal CJ, Jobling MG, Holmes RK, Hol WG (2005) Structural basis for the activation of cholera toxin by human ARF6-GTP. Science 309(5737):1093–1096

    Article  PubMed  CAS  Google Scholar 

  • Obata F, Tohyama K, Bonev AD, Kolling GL, Keepers TR, Gross LK, Nelson MT, Sato S, Obrig TG (2008) Shiga toxin 2 affects the central nervous system through receptor globotriaosylceramide localized to neurons. J Infect Dis 198(9):1398–1406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Obrig TG, Moran TP, Colinas RJ (1985) Ribonuclease activity associated with the 60S ribosome-inactivating proteins ricin A, phytolaccin and Shiga toxin. Biochem Biophys Res Commun 130(2):879–884

    Article  CAS  PubMed  Google Scholar 

  • Ogasawara T, Ito K, Igarashi K, Yutsudo T, Nakabayashi N, Takeda Y (1988) Inhibition of protein synthesis by a Vero toxin (VT2 or Shiga-like toxin II) produced by Escherichia coli O157:H7 at the level of elongation factor 1-dependent aminoacyl-tRNA binding to ribosomes. Microb Pathog 4(2):127–135

    Article  CAS  PubMed  Google Scholar 

  • Ohmura M, Yamasaki S, Kurazono H, Kashiwagi K, Igarashi K, Takeda Y (1993) Characterization of non-toxic mutant toxins of Vero toxin 1 that were constructed by replacing amino acids in the A subunit. Microb Pathog 15(3):169–176

    Article  CAS  PubMed  Google Scholar 

  • Okuda T, Tokuda N, Numata S, Ito M, Ohta M, Kawamura K, Wiels J, Urano T, Tajima O, Furukawa K, Furukawa K (2006) Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins. J Biol Chem 281(15):10230–10235

    Article  CAS  PubMed  Google Scholar 

  • Olsnes S, Reisbig R, Eiklid K (1981) Subunit structure of Shigella cytotoxin. J Biol Chem 256(16):8732–8738

    CAS  PubMed  Google Scholar 

  • Paton AW, Srimanote P, Talbot UM, Wang H, Paton JC (2004) A new family of potent AB(5) cytotoxins produced by Shiga toxigenic Escherichia coli. J Exp Med 200(1):35–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paton AW, Beddoe T, Thorpe CM, Whisstock JC, Wilce MC, Rossjohn J, Talbot UM, Paton JC (2006) AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP. Nature 443(7111):548–552

    Article  CAS  PubMed  Google Scholar 

  • PDB Research Collaboratory for Structural Bioinformatics (RCSB) Protein database (PDB). http://www.rcsb.org/pdb/home/home.do

  • Pellino CA, Karve SS, Pradhan S, Weiss AA (2016) AB5 preassembly is not required for Shiga toxin activity. J Bacteriol 198(11):1621–1630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pellizzari A, Pang H, Lingwood CA (1992) Binding of verocytotoxin 1 to its receptor is influenced by differences in receptor fatty acid content. Biochemistry 31(5):1363–1370

    Article  CAS  PubMed  Google Scholar 

  • Pepys MB, Baltz ML, de Beer FC, Dyck RF, Holford S, Breathnach SM, Black MM, Tribe CR, Evans DJ, Feinstein A (1982) Biology of serum amyloid P component. Ann N Y Acad Sci 389:286–298

    Article  CAS  PubMed  Google Scholar 

  • Pickett CL, Weinstein DL, Holmes RK (1987) Genetics of type IIa heat-labile enterotoxin of Escherichia coli: operon fusions, nucleotide sequence, and hybridization studies. J Bacteriol 169(11):5180–5187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pickett CL, Twiddy EM, Coker C, Holmes RK (1989) Cloning, nucleotide sequence, and hybridization studies of the type IIb heat-labile enterotoxin gene of Escherichia coli. J Bacteriol 171(9):4945–4952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pruimboom-Brees IM, Morgan TW, Ackermann MR, Nystrom ED, Samuel JE, Cornick NA, Moon HW (2000) Cattle lack vascular receptors for Escherichia coli O157:H7 Shiga toxins. Proc Natl Acad Sci U S A 97(19):10325–10329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • PyMOL PyMOL: A molecular visualization system on an open source foundation, maintained and distributed by Schrödinger. https://www.pymol.org/

  • Reisbig R, Olsnes S, Eiklid K (1981) The cytotoxic activity of Shigella toxin. Evidence for catalytic inactivation of the 60S ribosomal subunit. J Biol Chem 256(16):8739–8744

    CAS  PubMed  Google Scholar 

  • Ren J, Utsunomiya I, Taguchi K, Ariga T, Tai T, Ihara Y, Miyatake T (1999) Localization of verotoxin receptors in nervous system. Brain Res 825(1–2):183–188

    Article  CAS  PubMed  Google Scholar 

  • Romer W, Berland L, Chambon V, Gaus K, Windschiegl B, Tenza D, Aly MR, Fraisier V, Florent JC, Perrais D, Lamaze C, Raposo G, Steinem C, Sens P, Bassereau P, Johannes L (2007) Shiga toxin induces tubular membrane invaginations for its uptake into cells. Nature 450(7170):670–675

    Article  PubMed  CAS  Google Scholar 

  • Sandvig K, Garred O, Prydz K, Kozlov JV, Hansen SH, van Deurs B (1992) Retrograde transport of endocytosed Shiga toxin to the endoplasmic reticulum. Nature 358(6386):510–512

    Article  CAS  PubMed  Google Scholar 

  • Sandvig K, Spilsberg B, Lauvrak SU, Torgersen ML, Iversen TG, van Deurs B (2004) Pathways followed by protein toxins into cells. Int J Med Microbiol 293(7–8):483–490

    Article  CAS  PubMed  Google Scholar 

  • Sandvig K, Bergan J, Dyve AB, Skotland T, Torgersen ML (2010a) Endocytosis and retrograde transport of Shiga toxin. Toxicon 56(7):1181–1185

    Article  CAS  PubMed  Google Scholar 

  • Sandvig K, Torgersen ML, Engedal N, Skotland T, Iversen TG (2010b) Protein toxins from plants and bacteria: probes for intracellular transport and tools in medicine. FEBS Lett 584(12):2626–2634

    Article  CAS  PubMed  Google Scholar 

  • Sandvig K, Pust S, Skotland T, van Deurs B (2011) Clathrin-independent endocytosis: mechanisms and function. Curr Opin Cell Biol 23(4):413–420

    Article  CAS  PubMed  Google Scholar 

  • Saxena SK, O’Brien AD, Ackerman EJ (1989) Shiga toxin, Shiga-like toxin II variant, and ricin are all single-site RNA N-glycosidases of 28S RNA when microinjected into Xenopus oocytes. J Biol Chem 264(1):596–601

    CAS  PubMed  Google Scholar 

  • Scheutz F, Teel LD, Beutin L, Pierard D, Buvens G, Karch H, Mellmann A, Caprioli A, Tozzoli R, Morabito S, Strockbine NA, Melton-Celsa AR, Sanchez M, Persson S, O’Brien AD (2012) Multicenter evaluation of a sequence-based protocol for subtyping Shiga toxins and standardizing Stx nomenclature. J Clin Microbiol 50(9):2951–2963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scotland SM, Willshaw GA, Smith HR, Rowe B (1987) Properties of strains of Escherichia coli belonging to serogroup O157 with special reference to production of Vero cytotoxins VT1 and VT2. Epidemiol Infect 99(3):613–624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimizu T, Kawakami S, Sato T, Sasaki T, Higashide M, Hamabata T, Ohta T, Noda M (2007) The serine 31 residue of the B subunit of Shiga toxin 2 is essential for secretion in enterohemorrhagic Escherichia coli. Infect Immun 75(5):2189–2200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sixma TK, Kalk KH, van Zanten BA, Dauter Z, Kingma J, Witholt B, Hol WG (1993) Refined structure of Escherichia coli heat-labile enterotoxin, a close relative of cholera toxin. J Mol Biol 230(3):890–918

    Article  CAS  PubMed  Google Scholar 

  • Skinner C, McMahon S, Rasooly R, Carter JM, He X (2013) Purification and characterization of Shiga toxin 2f, an immunologically unrelated subtype of Shiga toxin 2. PLoS One 8(3):e59760. doi:10.1371/journal.pone.0059760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Skinner C, Patfield S, Stanker LH, Fratamico P, He X (2014) New high-affinity monoclonal antibodies against Shiga toxin 1 facilitate the detection of hybrid Stx1/Stx2 in vivo. PLoS One 9(6):e99854

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Smith DC, Sillence DJ, Falguieres T, Jarvis RM, Johannes L, Lord JM, Platt FM, Roberts LM (2006) The association of Shiga-like toxin with detergent-resistant membranes is modulated by glucosylceramide and is an essential requirement in the endoplasmic reticulum for a cytotoxic effect. Mol Biol Cell 17(3):1375–1387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soltyk AM, MacKenzie CR, Wolski VM, Hirama T, Kitov PI, Bundle DR, Brunton JL (2002) A mutational analysis of the globotriaosylceramide-binding sites of verotoxin VT1. J Biol Chem 277(7):5351–5359

    Article  CAS  PubMed  Google Scholar 

  • Speirs JI, Stavric S, Konowalchuk J (1977) Assay of Escherichia coli heat-labile enterotoxin with Vero cells. Infect Immun 16(2):617–622

    CAS  PubMed  PubMed Central  Google Scholar 

  • Strockbine NA, Marques LR, Newland JW, Smith HW, Holmes RK, O’Brien AD (1986) Two toxin-converting phages from Escherichia coli O157:H7 strain 933 encode antigenically distinct toxins with similar biologic activities. Infect Immun 53(1):135–140

    CAS  PubMed  PubMed Central  Google Scholar 

  • Strockbine NA, Jackson MP, Sung LM, Holmes RK, O’Brien AD (1988) Cloning and sequencing of the genes for Shiga toxin from Shigella dysenteriae type 1. J Bacteriol 170(3):1116–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suhan ML, Hovde CJ (1998) Disruption of an internal membrane-spanning region in Shiga toxin 1 reduces cytotoxicity. Infect Immun 66(11):5252–5259

    CAS  PubMed  PubMed Central  Google Scholar 

  • Takenouchi H, Kiyokawa N, Taguchi T, Matsui J, Katagiri YU, Okita H, Okuda K, Fujimoto J (2004) Shiga toxin binding to globotriaosyl ceramide induces intracellular signals that mediate cytoskeleton remodeling in human renal carcinoma-derived cells. J Cell Sci 117(Pt 17):3911–3922

    Article  CAS  PubMed  Google Scholar 

  • Tam PJ, Lingwood CA (2007) Membrane cytosolic translocation of verotoxin A1 subunit in target cells. Microbiology 153(Pt 8):2700–2710

    Article  CAS  PubMed  Google Scholar 

  • Tam P, Mahfoud R, Nutikka A, Khine AA, Binnington B, Paroutis P, Lingwood C (2008) Differential intracellular transport and binding of verotoxin 1 and verotoxin 2 to globotriaosylceramide-containing lipid assemblies. J Cell Physiol 216(3):750–763

    Article  CAS  PubMed  Google Scholar 

  • Tesh VL (2010) The induction of apoptosis by Shiga toxins and ricin. Curr Top Microbiol Immunol 357:137–178

    Google Scholar 

  • Tesh VL, Burris JA, Owens JW, Gordon VM, Wadolkowski EA, O’Brien AD, Samuel JE (1993) Comparison of the relative toxicities of Shiga-like toxins type I and type II for mice. Infect Immun 61(8):3392–3402

    CAS  PubMed  PubMed Central  Google Scholar 

  • Torgersen ML, Walchli S, Grimmer S, Skanland SS, Sandvig K (2007) Protein kinase Cdelta is activated by Shiga toxin and regulates its transport. J Biol Chem 282(22):16317–16328

    Article  CAS  PubMed  Google Scholar 

  • Torgersen ML, Engedal N, Bergan J, Sandvig K (2010) The intracellular journey of Shiga toxins. Open Toxinol J 3:3–12

    Article  CAS  Google Scholar 

  • Trofa AF, Ueno-Olsen H, Oiwa R, Yoshikawa M (1999) Dr. Kiyoshi Shiga: discoverer of the dysentery bacillus. Clin Infect Dis 29(5):1303–1306

    Article  CAS  PubMed  Google Scholar 

  • Utskarpen A, Massol R, van Deurs B, Lauvrak SU, Kirchhausen T, Sandvig K (2010) Shiga toxin increases formation of clathrin-coated pits through Syk kinase. PLoS One 5(7):e10944

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Walchli S, Skanland SS, Gregers TF, Lauvrak SU, Torgersen ML, Ying M, Kuroda S, Maturana A, Sandvig K (2008) The Mitogen-activated protein kinase p38 links Shiga Toxin-dependent signaling and trafficking. Mol Biol Cell 19(1):95–104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walchli S, Aasheim HC, Skanland SS, Spilsberg B, Torgersen ML, Rosendal KR, Sandvig K (2009) Characterization of clathrin and Syk interaction upon Shiga toxin binding. Cell Signal 21(7):1161–1168

    Article  PubMed  CAS  Google Scholar 

  • Waldor MK, Mekalanos JJ (1996) Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272(5270):1910–1914

    Article  CAS  PubMed  Google Scholar 

  • Weinstein DL, Jackson MP, Perera LP, Holmes RK, O’Brien AD (1989) In vivo formation of hybrid toxins comprising Shiga toxin and the Shiga-like toxins and role of the B subunit in localization and cytotoxic activity. Infect Immun 57(12):3743–3750

    CAS  PubMed  PubMed Central  Google Scholar 

  • Werber D, Fruth A, Buchholz U, Prager R, Kramer MH, Ammon A, Tschape H (2003) Strong association between Shiga toxin-producing Escherichia coli O157 and virulence genes stx2 and eae as possible explanation for predominance of serogroup O157 in patients with haemolytic uraemic syndrome. Eur J Clin Microbiol Infect Dis 22(12):726–730

    Article  CAS  PubMed  Google Scholar 

  • West RE Jr, Moss J, Vaughan M, Liu T, Liu TY (1985) Pertussis toxin-catalyzed ADP-ribosylation of transducin. Cysteine 347 is the ADP-ribose acceptor site. J Biol Chem 260(27):14428–14430

    CAS  PubMed  Google Scholar 

  • Yamasaki S, Furutani M, Ito K, Igarashi K, Nishibuchi M, Takeda Y (1991) Importance of arginine at position 170 of the A subunit of Vero toxin 1 produced by enterohemorrhagic Escherichia coli for toxin activity. Microb Pathog 11(1):1–9

    Article  CAS  PubMed  Google Scholar 

  • Yasumura Y, Kawakita Y (1988) Studies on SV40 in tissue culture: preliminary step for cancer research in vitro. In: Simizu B, Terasima T (eds) Vero cells - origin, properties and biomedical applications. Department of Microbiology, School of Medicine Chiba University, Chiba, pp 1–19

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. United States Department of Agriculture, Agricultural Research Service, Western Regional Research Center, Albany, CA, USA

    Christopher J. Silva, David L. Brandon, Craig B. Skinner & Xiaohua He

Authors
  1. Christopher J. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David L. Brandon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Craig B. Skinner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaohua He
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Silva, C.J., Brandon, D.L., Skinner, C.B., He, X. (2017). Structure of Shiga Toxins and Other AB5 Toxins. In: Shiga toxins. Food Microbiology and Food Safety(). Springer, Cham. https://doi.org/10.1007/978-3-319-50580-0_3

Download citation

Publish with us

Policies and ethics

Search

Navigation