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Structure. 2017 Aug 1;25(8):1233-1241.e3. doi: 10.1016/j.str.2017.06.004. Epub 2017 Jul 6.

The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel.

Author information

1
Department of Structural Biology, The Weizmann Institute of Science, Rehovot 7610001, Israel.
2
The Ilana and Pascal Mantoux Institute for Bioinformatics, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 7610001, Israel.
3
Department of Veterinary Disease Biology, University of Copenhagen, 1870 Frederiksbergc, Denmark.
4
Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, MD 21250, USA.
5
Department of Structural Biology, The Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: ada.yonath@weizmann.ac.il.

Abstract

Erythromycin is a clinically useful antibiotic that binds to an rRNA pocket in the ribosomal exit tunnel. Commonly, resistance to erythromycin is acquired by alterations of rRNA nucleotides that interact with the drug. Mutations in the β hairpin of ribosomal protein uL22, which is rather distal to the erythromycin binding site, also generate resistance to the antibiotic. We have determined the crystal structure of the large ribosomal subunit from Deinococcus radiodurans with a three amino acid insertion within the β hairpin of uL22 that renders resistance to erythromycin. The structure reveals a shift of the β hairpin of the mutated uL22 toward the interior of the exit tunnel, triggering a cascade of structural alterations of rRNA nucleotides that propagate to the erythromycin binding pocket. Our findings support recent studies showing that the interactions between uL22 and specific sequences within nascent chains trigger conformational rearrangements in the exit tunnel.

KEYWORDS:

antibiotics; erythromycin; macrolides; resistance; ribosomal protein uL22; ribosomes; tunnel

PMID:
28689968
DOI:
10.1016/j.str.2017.06.004
[Indexed for MEDLINE]
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