Structural insight into the role of the ribosomal tunnel in cellular regulation(383 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: Not available.
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
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Structural insight into the role of the ribosomal tunnel in cellular regulation