The Ribosomal Protein uL22 Modulates the Shape of the Protein Exit Tunnel
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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 E.
I: Structure, Bind 25, Nr. 8, 2017, s. 1233-1241.e3.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 E.
PY - 2017
Y1 - 2017
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.
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.
KW - antibiotics
KW - erythromycin
KW - macrolides
KW - resistance
KW - ribosomal protein uL22
KW - ribosomes
KW - tunnel
U2 - 10.1016/j.str.2017.06.004
DO - 10.1016/j.str.2017.06.004
M3 - Journal article
C2 - 28689968
AN - SCOPUS:85021826392
VL - 25
SP - 1233-1241.e3
JO - Structure
JF - Structure
SN - 0969-2126
IS - 8
ER -
ID: 182092348