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Structural basis for the NAD-hydrolysis mechanism and the ARTT-loop plasticity of C3 exoenzymes.

Ménétrey J, Flatau G, Boquet P, Ménez A, Stura EA
Protein Sci 17 878-86 (2008)
Related entries: 1gze, 1gzf, 2c89, 2c8a, 2c8b, 2c8c, 2c8d, 2c8e

Cited: 24 times
EuropePMC logo PMID: 18369192

Abstract

C3-like exoenzymes are ADP-ribosyltransferases that specifically modify some Rho GTPase proteins, leading to their sequestration in the cytoplasm, and thus inhibiting their regulatory activity on the actin cytoskeleton. This modification process goes through three sequential steps involving NAD-hydrolysis, Rho recognition, and binding, leading to Rho ADP-ribosylation. Independently, three distinct residues within the ARTT loop of the C3 exoenzymes are critical for each of these steps. Supporting the critical role of the ARTT loop, we have shown previously that it adopts a distinct conformation upon NAD binding. Here, we present seven wild-type and ARTT loop-mutant structures of C3 exoenzyme of Clostridium botulinum free and bound to its true substrate, NAD, and to its NAD-hydrolysis product, nicotinamide. Altogether, these structures expand our understanding of the conformational diversity of the C3 exoenzyme, mainly within the ARTT loop.

Articles - 2c8f mentioned but not cited (4)

  1. C3larvin toxin, an ADP-ribosyltransferase from Paenibacillus larvae. Krska D, Ravulapalli R, Fieldhouse RJ, Lugo MR, Merrill AR. J Biol Chem 290 1639-1653 (2015)
  2. Structural basis for the NAD-hydrolysis mechanism and the ARTT-loop plasticity of C3 exoenzymes. Ménétrey J, Flatau G, Boquet P, Ménez A, Stura EA. Protein Sci 17 878-886 (2008)
  3. An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins. Lugo MR, Merrill AR. Toxins (Basel) 11 E365 (2019)
  4. The N-terminus of Paenibacillus larvae C3larvinA modulates catalytic efficiency. Turner M, Heney KA, Merrill AR. Biosci Rep 41 BSR20203727 (2021)


Reviews citing this publication (4)

  1. Clostridial toxins. Popoff MR, Bouvet P. Future Microbiol 4 1021-1064 (2009)
  2. ADP-ribosylation of arginine. Laing S, Unger M, Koch-Nolte F, Haag F. Amino Acids 41 257-269 (2011)
  3. Therapeutic effects of Clostridium botulinum C3 exoenzyme. Just I, Rohrbeck A, Huelsenbeck SC, Hoeltje M. Naunyn Schmiedebergs Arch Pharmacol 383 247-252 (2011)
  4. Conformational plasticity is crucial for C3-RhoA complex formation by ARTT-loop. Tsuge H, Yoshida T, Tsurumura T. Pathog Dis 73 ftv094 (2015)

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  1. RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock. Mikelis CM, Simaan M, Ando K, Fukuhara S, Sakurai A, Amornphimoltham P, Masedunskas A, Weigert R, Chavakis T, Adams RH, Offermanns S, Mochizuki N, Zheng Y, Gutkind JS. Nat Commun 6 6725 (2015)
  2. Structure function analysis of an ADP-ribosyltransferase type III effector and its RNA-binding target in plant immunity. Jeong BR, Lin Y, Joe A, Guo M, Korneli C, Yang H, Wang P, Yu M, Cerny RL, Staiger D, Alfano JR, Xu Y. J Biol Chem 286 43272-43281 (2011)
  3. Arginine ADP-ribosylation mechanism based on structural snapshots of iota-toxin and actin complex. Tsurumura T, Tsumori Y, Qiu H, Oda M, Sakurai J, Nagahama M, Tsuge H. Proc Natl Acad Sci U S A 110 4267-4272 (2013)
  4. Cholera- and anthrax-like toxins are among several new ADP-ribosyltransferases. Fieldhouse RJ, Turgeon Z, White D, Merrill AR. PLoS Comput Biol 6 e1001029 (2010)
  5. Characterization of the toxin Plx2A, a RhoA-targeting ADP-ribosyltransferase produced by the honey bee pathogen Paenibacillus larvae. Ebeling J, Fünfhaus A, Knispel H, Krska D, Ravulapalli R, Heney KA, Lugo MR, Merrill AR, Genersch E. Environ Microbiol 19 5100-5116 (2017)
  6. Minimal essential length of Clostridium botulinum C3 peptides to enhance neuronal regenerative growth and connectivity in a non-enzymatic mode. Loske P, Boato F, Hendrix S, Piepgras J, Just I, Ahnert-Hilger G, Höltje M. J Neurochem 120 1084-1096 (2012)
  7. Structure-function analyses of a pertussis-like toxin from pathogenic Escherichia coli reveal a distinct mechanism of inhibition of trimeric G-proteins. Littler DR, Ang SY, Moriel DG, Kocan M, Kleifeld O, Johnson MD, Tran MT, Paton AW, Paton JC, Summers RJ, Schembri MA, Rossjohn J, Beddoe T. J Biol Chem 292 15143-15158 (2017)
  8. Characterization of the catalytic signature of Scabin toxin, a DNA-targeting ADP-ribosyltransferase. Lyons B, Lugo MR, Carlin S, Lidster T, Merrill AR. Biochem J 475 225-245 (2018)
  9. Dynamics of Scabin toxin. A proposal for the binding mode of the DNA substrate. Lugo MR, Lyons B, Lento C, Wilson DJ, Merrill AR. PLoS One 13 e0194425 (2018)
  10. Structure-function discrepancy in Clostridium botulinum C3 toxin for its rational prioritization as a subunit vaccine. Prathiviraj R, Prisilla A, Chellapandi P. J Biomol Struct Dyn 34 1317-1329 (2016)
  11. Structural constraints-based evaluation of immunogenic avirulent toxins from Clostridium botulinum C2 and C3 toxins as subunit vaccines. Prisilla A, Prathiviraj R, Sasikala R, Chellapandi P. Infect Genet Evol 44 17-27 (2016)
  12. A mutational analysis of residues in cholera toxin A1 necessary for interaction with its substrate, the stimulatory G protein Gsα. Jobling MG, Gotow LF, Yang Z, Holmes RK. Toxins (Basel) 7 919-935 (2015)
  13. Molecular Evolutionary Constraints that Determine the Avirulence State of Clostridium botulinum C2 Toxin. Prisilla A, Prathiviraj R, Chellapandi P. J Mol Evol 84 174-186 (2017)
  14. Mapping the DNA-Binding Motif of Scabin Toxin, a Guanine Modifying Enzyme from Streptomyces scabies. Vatta M, Lyons B, Heney KA, Lidster T, Merrill AR. Toxins (Basel) 13 55 (2021)
  15. Crystal structures of pertussis toxin with NAD+ and analogs provide structural insights into the mechanism of its cytosolic ADP-ribosylation activity. Sakari M, Tran MT, Rossjohn J, Pulliainen AT, Beddoe T, Littler DR. J Biol Chem 298 101892 (2022)
  16. Potentiation of Brain-Derived Neurotrophic Factor-Induced Protection of Spiral Ganglion Neurons by C3 Exoenzyme/Rho Inhibitor. Harre J, Heinkele L, Steffens M, Warnecke A, Lenarz T, Just I, Rohrbeck A. Front Cell Neurosci 15 602897 (2021)


Related citations provided by authors (1)

  1. NAD binding induces conformational changes in Rho ADP-ribosylating clostridium botulinum C3 exoenzyme.. Ménétrey J, Flatau G, Stura EA, Charbonnier JB, Gas F, Teulon JM, Le Du MH, Boquet P, Menez A J Biol Chem 277 30950-7 (2002)

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