A chemical genomic screen in Saccharomyces cerevisiae reveals a role for diphthamidation of translation elongation factor 2 in inhibition of protein synthesis by sordarin

Antimicrobial Agents and Chemotherapy

Volumn 52, Issue 5, 2008, Pages 1623-1629

  Botet, Javier ^a   Rodríguez Mateos, María ^b   Ballesta, Juan P G ^b   Revuelta, José Luis ^a   Remacha, Miguel ^b  

^a UNIVERSITY OF SALAMANCA   (Spain)

^b UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

DIPHTHAMIDE; ELONGATION FACTOR 2; HISTIDINE DERIVATIVE; SORDARIN;

ADENOSINE DIPHOSPHATE RIBOSYLATION; AMIDATION; ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; FUNGAL CELL; FUNGAL GENE; FUNGUS GROWTH; FUNGUS MUTANT; GENE DELETION; GENOME ANALYSIS; HAPLOIDY; HIGH THROUGHPUT SCREENING; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN SYNTHESIS INHIBITION; SACCHAROMYCES CEREVISIAE;

ELECTROPHORESIS, POLYACRYLAMIDE GEL; GENOMICS; INDENES; MUTATION; PEPTIDE ELONGATION FACTOR 2; PROTEIN BIOSYNTHESIS; PROTEIN SYNTHESIS INHIBITORS; SACCHAROMYCES CEREVISIAE;

EID: 42949164918     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.01603-07     Document Type: Article

References (49)

1. Andersen, C. B., T. Becker, M. Blau, M. Anand, M. Halic, B. Balar, T. Mielke, T. Boesen, J. S. Pedersen, C. M. Spahn, T. G. Kinzy, G. R. Andersen, and R. Beckmann. 2006. Structure of eEF3 and the mechanism of transfer RNA release from the E-site. Nature 443:663-668.
2. Ashburner, M., C. A. Ball, J. A. Blake, D. Botstein, H. Butler, J. M. Cherry, A. P. Davis, K. Dolinski, S. S. Dwight, J. T. Eppig, M. A. Harris, D. P. Hill, L. Issel-Tarver, A. Kasarskis, S. Lewis, J. C. Matese, J. E. Richardson, M. Ringwald, G. M. Rubin, G. Sherlock, et al. 2000. Gene ontology: tool for the unification of biology. Nat. Genet. 25:25-29.
3. Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248-254.
4. Briones, E., C. Briones, M. Remacha, and J. P. Ballesta. 1998. The GTPase center protein L12 is required for correct ribosomal stalk assembly but not for Saccharomyces cerevisiae viability. J. Biol. Chem. 273:31956-31961.
5. Capa, L., A. Mendoza, J. L. Lavandera, F. Gomez de las Heras, and J. F. García-Bustos. 1998. Translation elongation factor 2 is part of the target for a new family of antifungals. Antimicrob. Agents Chemother. 42:2694-2699.
6. Dominguez, J. M., V. A. Kelly, O. S. Kinsman, M. S. Marriott, F. Gomez de las Heras, and J. J. Martin. 1998. Sordarins: a new class of antifungals with selective inhibition of the protein synthesis elongation cycle in yeasts. Antimicrob. Agents Chemother. 42:2274-2278.
7. Dominguez, J. M., and J. J. Martin. 1998. Identification of elongation factor 2 as the essential protein targeted by sordarins in Candida albicans. Antimicrob. Agents Chemother. 42:2279-2283.
8. Fichtner, L., D. Jablonowski, A. Schierhorn, H. K. Kitamoto, M. J. Stark, and R. Schaffrath. 2003. Elongator's toxin-target (TOT) function is nuclear localization sequence dependent and suppressed by post-translational modification. Mol. Microbiol. 49:1297-1307.
9. Fichtner, L., and R. Schaffrath. 2002. KTI11 and KTI13, Saccharomyces cerevisiae genes controlling sensitivity to G1 arrest induced by Kluyveromyces lactis zymocin. Mol. Microbiol. 44:865-875.
10. Giaever, G., A. M. Chu, L. Ni, C. Connelly, L. Riles, S. Veronneau, S. Dow, A. Lucau-Danila, K. Anderson, B. Andre, A. P. Arkin, A. Astromoff, M. El-Bakkoury, R. Bangham, R. Benito, S. Brachat, S. Campanaro, M. Curtiss, K. Davis, A. Deutschbauer, K. D. Entian, P. Flaherty, F. Foury, D. J. Garfinkel, M. Gerstein, D. Gotte, U. Guidener, J. H. Hegemann, S. Hempel, Z. Herman, D. F. Jaramillo, D. E. Kelly, S. L. Kelly, P. Kotter, D. LaBonte, D. C. Lamb, N. Lan, H. Liang, H. Liao, L. Liu, C. Luo, M. Lussier, R. Mao, P. Menard, S. L. Ooi, J. L. Revuelta, C. J. Roberts, M. Rose, P. Ross-Macdonald, B. Scherens, G. Schimmack, B. Shafer, D. D. Shoemaker, S. Sookhai-Mahadeo, R. K. Storms, J. N. Strathern, G. Valle, M. Voet, G. Volckaert, C. Y. Wang, T. R. Ward, J. Wilhelmy, E. A. Winzeler, Y. Yang, G. Yen, E. Youngman, K. Yu, H. Bussey, J. D. Boeke, M. Snyder, P. Philippsen, R. W. Davis, and M. Johnston. 2002. Functional profiling of the Saccharomyces cerevisiae genome. Nature 418:387-391.
11. Gietz, R. D., and R. A. Woods. 2002. Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method. Methods Enzymol. 350:87-96.
12. Goldring, E. S., L. I. Grossman, D. Krupnick, D. R. Cryer, and J. Marmur. 1970. The petite mutation in yeast. Loss of mitochondrial deoxyribonucleic acid during induction of petites with ethidium bromide. J. Mol. Biol. 52:323-335.
13. Gomez-Lorenzo, M. G., and J. F. Garcia-Bustos. 1998. Ribosomal P-protein stalk function is targeted by sordarin antifungals. J. Biol. Chem. 273:25041-25044.
14. Gomez-Lorenzo, M. G., C. M. Spahn, R. K. Agrawal, R. A. Grassucci, P. Penczek, K. Chakraburtty, J. P. Ballesta, J. L. Lavandera, J. F. Garcia-Bustos, and J. Frank. 2000. Three-dimensional cryo-electron microscopy localization of EF2 in the Saccharomyces cerevisiae 80S ribosome at 17.5 A resolution. EMBO J. 19:2710-2718.
15. Herreros, E., C. M. Martinez, M. J. Almela, M. S. Marriott, F. G. De Las Heras, and D. Gargallo-Viola. 1998. Sordarins: in vitro activities of new antifungal derivatives against pathogenic yeasts, Pneumocystis carinii, and filamentous fungi. Antimicrob. Agents Chemother. 42:2863-2869.
16. Huang, B., M. J. Johansson, and A. S. Bystrom. 2005. An early step in wobble uridine tRNA modification requires the Elongator complex. RNA 11:424-436.
17. Jablonowski, D., S. Zink, C. Mehlgarten, G. Daum, and R. Schaffrath. 2006. tRNAGlu wobble uridine methylation by Trm9 identifies Elongator's key role for zymocin-induced cell death in yeast. Mol. Microbiol. 59:677-688.
18. Jorgensen, R., A. R. Merrill, S. P. Yates, V. E. Marquez, A. L. Schwan, T. Boesen, and G. R. Andersen. 2005. Exotoxin A-eEF2 complex structure indicates ADP ribosylation by ribosome mimicry. Nature 436:979-984.
19. Jorgensen, R., P. A. Ortiz, A. Carr-Schmid, P. Nissen, T. G. Kinzy, and G. R. Andersen. 2003. Two crystal structures demonstrate large conformational changes in the eukaryotic ribosomal translocase. Nat. Struct. Mol. Biol. 10:379-385.
20. Jorgensen, R., S. P. Yates, D. J. Teal, J. Nilsson, G. A. Prentice, A. R. Merrill, and G. R. Andersen. 2004. Crystal structure of ADP-ribosylated ribosomal translocase from Saccharomyces cerevisiae. J. Biol. Chem. 279:45919-45925.
21. Justice, M. C., M. J. Hsu, B. Tse, T. Ku, J. Balkovec, D. Schmatz, and J. Nielsen. 1998. Elongation factor 2 as a novel target for selective inhibition of fungal protein synthesis. J. Biol. Chem. 273:3148-3151.
22. Justice, M. C., T. Ku, M. J. Hsu, K. Carniol, D. Schmatz, and J. Nielsen. 1999. Mutations in ribosomal protein L10e confer resistance to the fungal-specific eukaryotic elongation factor 2 inhibitor sordarin. J. Biol. Chem. 274:4869-4875.
23. Killeen, K. P., V. Escuyer, J. J. Mekalanos, and R. J. Collier. 1992. Reversion of recombinant toxoids: mutations in diphtheria toxin that partially compensate for active-site deletions. Proc. Natl. Acad. Sci. USA 89:6207-6209.
24. Kinsman, O. S., P. A. Chalk, H. C. Jackson, R. F. Middleton, A. Shuttle worth, B. A. Rudd, C. A. Jones, H. M. Noble, H. G. Wildman, M. J. Dawson, C. Stylli, P. J. Sidebottom, B. Lamont, S. Lynn, and M. V. Hayes. 1998. Isolation and characterisation of an antifungal antibiotic (GR135402) with protein synthesis inhibition. J. Antibiot. 51:41-49.
25. Komili, S., N. G. Farny, F. P. Roth, and P. A. Silver. 2007. Functional specificity among ribosomal proteins regulates gene expression. Cell 131: 557-571.
26. Liu, S., G. T. Milne, J. G. Kuremsky, G. R. Fink, and S. H. Leppla. 2004. Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2. Mol. Cell. Biol. 24:9487-9497.
27. Mager, W. H., and J. Winderickx. 2005. Yeast as a model for medical and medicinal research. Trends Pharmacol. Sci. 26:265-273.
28. Martinez, A., P. Aviles, E. Jimenez, J. Caballero, and D. Gargallo-Viola. 2000. Activities of sordarins in experimental models of candidiasis, aspergillosis, and pneumocystosis. Antimicrob. Agents Chemother. 44:3389-3394.
29. Mattheakis, L. C., W. H. Shen, and R. J. Collier. 1992. DPH5, a methyl-transferase gene required for diphthamide biosynthesis in Saccharomyces cerevisiae. Mol. Cell. Biol. 12:4026-4037.
30. Mattheakis, L. C., F. Sor, and R. J. Collier. 1993. Diphthamide synthesis in Saccharomyces cerevisiae: structure of the DPH2 gene. Gene 132:149-154.
31. McDermott, P. F., R. D. Walker, and D. G. White. 2003. Antimicrobials: modes of action and mechanisms of resistance. Int. J. Toxicol. 22:135-143.
32. Morishita, R., A. Kawagoshi, T. Sawasaki, K. Madin, T. Ogasawara, T. Oka, and Y. Endo. 1999. Ribonuclease activity of rat liver perchloric acid-soluble protein, a potent inhibitor of protein synthesis. J. Biol. Chem. 274:20688-20692.
33. Ortiz, P. A., R. Ulloque, G. K. Kihara, H. Zheng, and T. G. Kinzy. 2006. Translation elongation factor 2 anticodon mimicry domain mutants affect fidelity and diphtheria toxin resistance. J. Biol. Chem. 281:32639-32648.
34. Petitjean, A., N. Bonneaud, and F. Lacroute. 1995. The duplicated Saccharomyces cerevisiae gene SSM1 encodes a eucaryotic homolog of the eubacterial and archaebacterial L1 ribosomal proteins. Mol. Cell. Biol. 15:5071-5081.
35. Remacha, M., A. Jimenez-Diaz, B. Bermejo, M. A. Rodriguez-Gabriel, E. Guarinos, and J. P. Ballesta. 1995. Ribosomal acidic phosphoproteins P1 and P2 are not required for cell viability but regulate the pattern of protein expression in Saccharomyces cerevisiae. Mol. Cell. Biol. 15:4754-4762.
36. Robinson, M. D., J. Grigull, N. Mohammad, and T. R. Hughes. 2002. FunSpec: a web-based cluster interpreter for yeast. BMC Bioinformatics 3:35.
37. Rodriguez-Gabriel, M. A., M. Remacha, and J. P. Ballesta. 1998. Phosphorylation of ribosomal protein P0 is not essential for ribosome function but can affect translation. Biochemistry 37:16620-16626.
38. Sambrook, J., and D. W. Russell. 2001. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
39. Santos, C., and J. P. Ballesta. 2002. Role of the ribosomal stalk components in the resistance of Aspergillus fumigatus to the sordarin antifungals. Mol. Microbiol. 43:227-237.
40. Santos, C., M. A. Rodriguez-Gabriel, M. Remacha, and J. P. G. Ballesta. 2004. Ribosomal P0 protein domain involved in selectivity of antifungal sordarin derivatives. Antimicrob. Agents Chemother. 48:2930-2936.
41. Shastry, M., J. Nielsen, T. Ku, M. J. Hsu, P. Liberator, J. Anderson, D. Schmatz, and M. C. Justice. 2001. Species-specific inhibition of fungal protein synthesis by sordarin: identification of a sordarin-specificity region in eukaryotic elongation factor 2. Microbiology 147:383-390.
42. Spahn, C. M., M. G. Gomez-Lorenzo, R. A. Grassucci, R. Jorgensen, G. R. Andersen, R. Beckmann, P. A. Penczek, J. P. Ballesta, and J. Frank. 2004. Domain movements of elongation factor eEF2 and the eukaryotic 80S ribosome facilitate tRNA translocation. EMBO J. 23:1008-1019.
43. Steinmetz, L. M., C. Scharfe, A. M. Deutschbauer, D. Mokranjac, Z. S. Herman, T. Jones, A. M. Chu, G. Giaever, H. Prokisch, P. J. Oefner, and R. W. Davis. 2002. Systematic screen for human disease genes in yeast. Nat. Genet. 31:400-404.
44. Sturgeon, C. M., D. Kemmer, H. J. Anderson, and M. Roberge. 2006. Yeast as a tool to uncover the cellular targets of drugs. Biotechnol. J. 1:289-298.
45. Taylor, D. J., J. Nilsson, A. R. Merrill, G. R. Andersen, P. Nissen, and J. Frank. 2007. Structures of modified eEF2 80S ribosome complexes reveal the role of GTP hydrolysis in translocation. EMBO J. 26:2421-2431.
46. Valle, M., A. Zavialov, J. Sengupta, U. Rawat, M. Ehrenberg, and J. Frank. 2003. Locking and unlocking of ribosomal motions. Cell 114:123-134.
47. Van Ness, B., J. Howard, and J. Bodley. 1980. ADP-ribosylation of elongation factor 2 by diphtheria toxin. Isolation and properties of the novel ribosyl-amino acid and its hydrolysis products. J. Biol. Chem. 255:10717-10720.
48. Vilella, M. D., M. Remacha, B. L. Ortíz, E. Méndez, and J. P. G. Ballesta. 1991. Characterization of yeast acidic ribosomal phosphoproteins using monoclonal antibodies. Eur. J. Biochem. 196:407-414.
49. Winzeler, E. A., D. D. Shoemaker, A. Astromoff, H. Liang, K. Anderson, A. Andre, R. Bangham, R. Benito, and J. E. Boeke. 1999. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285:901-906.