Structural insight into the role of the ribosomal tunnel in cellular regulation(375 views) Berisio R, Schluenzen F, Harms J, Bashan A, Auerbach T, Baram D, Yonath A
Keywords: Antibiotic Agent, Azithromycin, Erythromycin, Macrolide, Ribosome Protein, Ribosome Rna, Troleandomycin, Article, Biosynthesis, Cell, Crystal Structure, Deinococcus Radiodurans, Drug Binding, Drug Protein Binding, Nonhuman, Priority Journal, Protein Structure, Regulatory Mechanism, Structure Analysis, Amino Acid Sequence, Crystallography, X-Ray, Models, Molecular, Molecular Sequence Data, Protein Conformation, Ribosomal Proteins, Signal Transduction,
Affiliations: *** IBB - CNR ***
Max-Planck-Res. U. Ribosomal Struct., Hamburg, Germany
Inst. of Biostructure and Bioimaging, CNR, Napoli, Italy
Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
Institute of Biochemistry, Free University, Berlin, Germany
References: Milligan, R.A., Unwin, P.N., Location of exit channel for nascent protein in 80S ribosome (1986) Nature, 319, pp. 693-69
Yonath, A., Leonard, K.R., Wittmann, H.G., A tunnel in the large ribosomal subunit revealed by three-dimensional image reconstruction (1987) Science, 236, pp. 813-816
Gabashvili, I.S., The polypeptide tunnel system in the ribosome and its gating in erythromycin resistant mutants of L 4 and L22 (2001) Mol. Cell, 8, pp. 181-188
Tenson, T., Ehrenberg, M., Regulatory nascent peptides in the ribosomal tunnel (2002) Cell, 108, pp. S91-S594
Morris, D.R., Geballe, A.P., Upstream open reading frames as regulators of mRNA translation (2000) Mol. Cell. Biol., 20, pp. 8635-8642
Sarker, S., Rudd, K.E., Oliver, D., Revised translation start site for secM defines an atypical signal peptide that regulates E. coli secA expression (2000) J. Bacteriol., 182, pp. 5592-5595
Nakatogawa, H., Ito, K., The ribosomal exit tunnel functions as a discriminating gate (2002) Cell, 108, pp. 629-636
Gong, F., Yanofsky, C., Instruction of translating ribosome by nascent peptide (2002) Science, 297, pp. 1864-1867
Stroud, R.M., Walter, P., Signal sequence recognition and protein targeting (1999) Curr. Opin. Struct. Biol., 9, pp. 754-759
Nissen, P., Hansen, J., Ban, N., Moore, P.B., Steitz, T.A., The structural basis of ribosome activity in peptide bond synthesis (2000) Science, 289, pp. 920-930
Harms, J., High resolution structure of the large ribosomal subunit from a mesophilic eubacterium (2001) Cell, 107, pp. 679-688
Unge, J., The crystal structure of ribosomal protein L22 from Thermus thermophilus: Insights into the mechanism of erythromycin resistance (1998) Structure, 6, pp. 1577-1586
Schluenzen, F., Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria (2001) Nature, 413, pp. 814-821
Hansen, J.L., The structures of four macrolide antibiotics bound to the large ribosomal subunit (2002) Mol. Cell, 10, pp. 117-128
Periti, P., Tonelli, F., Mazzei, T., Ficari, F., Antimicrobial chemoimmunoprophylaxis in colorectal surgery with cefotetan and thymostimulin: Prospective, controlled multicenter study (1993) J. Chemother., 5, pp. 37-42. , Italian Study Group on Antimicrobial Prophylaxis in Abdominal Surgery
Chepkwony, H.K., Roets, E., Hoogmartens, J., Liquid chromatography of troleandomycin (2001) J. Chromatogr. A, 914, pp. 53-58
Tenson, T., Mankin, A.S., Short peptides conferring resistance to macrolide antibiotics (2001) Peptides, 22, pp. 1661-1668
Verdier, L., Gharbi-Benarous, J., Bertho, G., Mauvais, P., Girault, J.P., Antibiotic resistance peptides: Interaction of peptides conferring macrolide and ketolide resistance with Staphylococcus aureus ribosomes: Conformation of bound peptides as determined by transferred NOE experiments (2002) Biochemistry, 41, pp. 4218-4229
Douthwaite, S., Hansen, L.H., Mauvais, P., Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain II of 23S rRNA (2000) Mol. Microbiol., 36, pp. 183-193
Weisblum, B., Erythromycin resistance by ribosome modification. Antimicrob (1995) Agents Chemother., 39, pp. 577-585
Xiong, L., Shah, S., Mauvais, P., Mankin, A.S., A ketolide resistance mutation in domain II of 23S rRNA reveals the proximity of hairpin 35 to the peptidyl transferase centre (1999) Mol. Microbiol., 31, pp. 633-639
Goldman, R.C., Fesik, S.W., Doran, C.C., Role of protonated and neutral forms of macrolides in binding to ribosomes from Gram-positive and Gram-negative bacteria (1990) Antimicrob. Agents Chemother., 34, pp. 426-431
Davydova, N., Streltsov, V., Wilce, M., Liljas, A., Garber, M., L 22 ribosomal protein and effect of its mutation on ribosome resistance to erythromycin (2002) J. Mol. Biol., 322, pp. 635-644
Liao, S., Lin, J., Do, H., Johnson, A.E., Both lumenal and cytosolic gating of the aqueous ER translocon pore are regulated from inside the ribosome during membrane protein integration (1997) Cell, 90, pp. 31-41
Stern, S., Moazed, D., Noller, H.F., Structural analysis of RNA using chemical and enzymatic probing monitored by primer extension (1988) Methods Enzymol., 164, pp. 481-489
Otwinowski, Z., Minor, W., Processing of X-ray diffraction data collected in oscillation mode (1997) Methods Enzymol., 276, pp. 307-326
Bailey, S., The CCP4 suite - Programs for protein crystallography (1994) Acta Crystallogr. D, 50, pp. 760-763
Brunger, A.T., Crystallography & NMR system: A new software suite for macromolecular structure determination (1998) Acta Crystallogr. D, 54, pp. 905-921
Jones, T.A., Zou, J.Y., Cowan, S.W., Kjeldgaard, M., Improved methods for building protein models in electron density maps and the location of errors in these models (1991) Acta Crystallogr. A, 47, pp. 110-119
Flocco, M.M., Mowbray, S.L., Cα-based torsion angles: A simple tool to analyze protein conformational changes (1995) Protein Sci., 4, pp. 2118-2122
Carson, M., Ribbons (1997) Methods Enzymol., 277, pp. 493-505
Wallace, A.C., Laskowski, R.A., Thornton, J.M., LIGPLOT a program to generate schematic diagrams of protein-ligand interactions (1995) Protein Eng., 8, pp. 127-134
Milligan, R. A., Unwin, P. N., Location of exit channel for nascent protein in 80S ribosome (1986) Nature, 319, pp. 693-69
Gabashvili, I. S., The polypeptide tunnel system in the ribosome and its gating in erythromycin resistant mutants of L 4 and L22 (2001) Mol. Cell, 8, pp. 181-188
Morris, D. R., Geballe, A. P., Upstream open reading frames as regulators of mRNA translation (2000) Mol. Cell. Biol., 20, pp. 8635-8642
Stroud, R. M., Walter, P., Signal sequence recognition and protein targeting (1999) Curr. Opin. Struct. Biol., 9, pp. 754-759
Hansen, J. L., The structures of four macrolide antibiotics bound to the large ribosomal subunit (2002) Mol. Cell, 10, pp. 117-128
Chepkwony, H. K., Roets, E., Hoogmartens, J., Liquid chromatography of troleandomycin (2001) J. Chromatogr. A, 914, pp. 53-58
Goldman, R. C., Fesik, S. W., Doran, C. C., Role of protonated and neutral forms of macrolides in binding to ribosomes from Gram-positive and Gram-negative bacteria (1990) Antimicrob. Agents Chemother., 34, pp. 426-431
Brunger, A. T., Crystallography & NMR system: A new software suite for macromolecular structure determination (1998) Acta Crystallogr. D, 54, pp. 905-921
Jones, T. A., Zou, J. Y., Cowan, S. W., Kjeldgaard, M., Improved methods for building protein models in electron density maps and the location of errors in these models (1991) Acta Crystallogr. A, 47, pp. 110-119
Flocco, M. M., Mowbray, S. L., C -based torsion angles: A simple tool to analyze protein conformational changes (1995) Protein Sci., 4, pp. 2118-2122
Wallace, A. C., Laskowski, R. A., Thornton, J. M., LIGPLOT a program to generate schematic diagrams of protein-ligand interactions (1995) Protein Eng., 8, pp. 127-134
Structural insight into the role of the ribosomal tunnel in cellular regulation
Nascent proteins emerge out of ribosomes through an exit tunnel, which was assumed to be a firmly built passive path. Recent biochemical results, however, indicate that the tunnel plays an active role in sequence-specific gating of nascent chains and in responding to cellular signals. Consistently, modulation of the tunnel shape, caused by the binding of the semi-synthetic macrolide troleandomycin to the large ribosomal subunit from Deinococcus radiodurans, was revealed crystallographically. The results provide insights into the tunnel dynamics at high resolution. Here we show that, in addition to the typical steric blockage of the ribosomal tunnel by macrolides, troleandomycin induces a conformational rearrangement in a wall constituent, protein L22, flipping the tip of its highly conserved β-hairpin across the tunnel. On the basis of mutations that alleviate elongation arrest, the tunnel motion could be correlated with sequence discrimination and gating, suggesting that specific arrest motifs within nascent chain sequences may induce a similar gating mechanism.
Structural insight into the role of the ribosomal tunnel in cellular regulation
No results.
Structural insight into the role of the ribosomal tunnel in cellular regulation