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

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

SN - 0969-2126

VL - 25

SP - 1233-1241.e3

JO - Structure

JF - Structure

IS - 8

ER -