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

Research output: Contribution to journalArticleResearchpeer-review

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, Itai ; Zimmerman, Ella ; Davidovich, Chen ; Belousoff, Matthew ; Matzov, Donna ; Krupkin, Miri ; Rozenberg, Haim ; Bashan, Anat ; Friedlander, Gilgi ; Kjeldgaard, Jette ; Ingmer, Hanne ; Lindahl, Lasse ; Zengel, Janice M. ; Yonath, Ada. / The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel. In: Structure. 2017 ; Vol. 25, No. 8. pp. 1233-1241.
@article{f2b5962c40a549888b7d8684589db78a,
title = "The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel",
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.",
keywords = "Antibiotics, Erythromycin, Macrolides, Resistance, Ribosomal protein uL22, Ribosomes, Tunnel",
author = "Itai Wekselman and Ella Zimmerman and Chen Davidovich and Matthew Belousoff and Donna Matzov and Miri Krupkin and Haim Rozenberg and Anat Bashan and Gilgi Friedlander and Jette Kjeldgaard and Hanne Ingmer and Lasse Lindahl and Zengel, {Janice M.} and Ada Yonath",
year = "2017",
month = "8",
day = "1",
doi = "10.1016/j.str.2017.06.004",
language = "English",
volume = "25",
pages = "1233--1241",
journal = "Structure",
issn = "0969-2126",
publisher = "Elsevier",
number = "8",

}

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, JM & Yonath, A 2017, 'The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel' Structure, vol. 25, no. 8, pp. 1233-1241. https://doi.org/10.1016/j.str.2017.06.004

The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel. / Wekselman, Itai; Zimmerman, Ella; Davidovich, Chen; Belousoff, Matthew; Matzov, Donna; Krupkin, Miri; Rozenberg, Haim; Bashan, Anat; Friedlander, Gilgi; Kjeldgaard, Jette; Ingmer, Hanne; Lindahl, Lasse; Zengel, Janice M.; Yonath, Ada.

In: Structure, Vol. 25, No. 8, 01.08.2017, p. 1233-1241.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel

AU - Wekselman, Itai

AU - Zimmerman, Ella

AU - Davidovich, Chen

AU - Belousoff, Matthew

AU - Matzov, Donna

AU - Krupkin, Miri

AU - Rozenberg, Haim

AU - Bashan, Anat

AU - Friedlander, Gilgi

AU - Kjeldgaard, Jette

AU - Ingmer, Hanne

AU - Lindahl, Lasse

AU - Zengel, Janice M.

AU - Yonath, Ada

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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.

AB - 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.

KW - Antibiotics

KW - Erythromycin

KW - Macrolides

KW - Resistance

KW - Ribosomal protein uL22

KW - Ribosomes

KW - Tunnel

UR - http://www.scopus.com/inward/record.url?scp=85021826392&partnerID=8YFLogxK

U2 - 10.1016/j.str.2017.06.004

DO - 10.1016/j.str.2017.06.004

M3 - Article

VL - 25

SP - 1233

EP - 1241

JO - Structure

JF - Structure

SN - 0969-2126

IS - 8

ER -