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

Itai Wekselman, Ella Zimmerman, Chen Davidovich, Matthew Belousoff, Donna Matzov, Miri Krupkin, Haim Rozenberg, Anat Bashan, Gilgi Friedlander, Jette Kjeldgaard, Hanne Ingmer, Lasse Lindahl, Janice M. Zengel, Ada Yonath

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8 Citations (Scopus)

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. Wekselman et al. report the crystal structure of the large ribosomal subunit with an insertion mutation in ribosomal protein uL22 that renders resistance to erythromycin. The mutation triggers structural rearrangements in the loop of uL22 and rRNA nucleotides in the exit tunnel that increase the flexibility of erythromycin binding pocket.

Original languageEnglish
Pages (from-to)1233-1241
Number of pages9
JournalStructure
Volume25
Issue number8
DOIs
Publication statusPublished - 1 Aug 2017
Externally publishedYes

Keywords

  • Antibiotics
  • Erythromycin
  • Macrolides
  • Resistance
  • Ribosomal protein uL22
  • Ribosomes
  • Tunnel

Cite this

Wekselman, I., Zimmerman, E., Davidovich, C., Belousoff, M., Matzov, D., Krupkin, M., Rozenberg, H., Bashan, A., Friedlander, G., Kjeldgaard, J., Ingmer, H., Lindahl, L., Zengel, J. M., & Yonath, A. (2017). The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel. Structure, 25(8), 1233-1241. https://doi.org/10.1016/j.str.2017.06.004