The structural basis for inhibition of ribosomal translocation by viomycin
| Autor: | Laura Lancaster, Ying-Hui Wang, Jie Zhou, Harry F. Noller, Xing Zhang, Ling Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Ribosomal Proteins Protein subunit Molecular Conformation Crystallography X-Ray Ribosome Viomycin 03 medical and health sciences RNA Transfer 23S ribosomal RNA Escherichia coli medicine 30S RNA Messenger Binding site 030304 developmental biology 0303 health sciences Multidisciplinary 030306 microbiology Chemistry Biological Sciences Ribosomal RNA Anti-Bacterial Agents RNA Ribosomal Protein Biosynthesis Transfer RNA Biophysics Ribosomes Protein Binding medicine.drug |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2002888117 |
| Popis: | Viomycin, an antibiotic that has been used to fight tuberculosis infections, is believed to block the translocation step of protein synthesis by inhibiting ribosomal subunit dissociation and trapping the ribosome in an intermediate state of intersubunit rotation. The mechanism by which viomycin stabilizes this state remains unexplained. To address this, we have determined cryo-EM and X-ray crystal structures of Escherichia coli 70S ribosome complexes trapped in a rotated state by viomycin. The 3.8-Å resolution cryo-EM structure reveals a ribosome trapped in the hybrid state with 8.6° intersubunit rotation and 5.3° rotation of the 30S subunit head domain, bearing a single P/E state transfer RNA (tRNA). We identify five different binding sites for viomycin, four of which have not been previously described. To resolve the details of their binding interactions, we solved the 3.1-Å crystal structure of a viomycin-bound ribosome complex, revealing that all five viomycins bind to ribosomal RNA. One of these (Vio1) corresponds to the single viomycin that was previously identified in a complex with a nonrotated classical-state ribosome. Three of the newly observed binding sites (Vio3, Vio4, and Vio5) are clustered at intersubunit bridges, consistent with the ability of viomycin to inhibit subunit dissociation. We propose that one or more of these same three viomycins induce intersubunit rotation by selectively binding the rotated state of the ribosome at dynamic elements of 16S and 23S rRNA, thus, blocking conformational changes associated with molecular movements that are required for translocation. |
| Databáze: | OpenAIRE |
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