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Structure of 23S rRNA hairpin 35 and its interaction with the tylosin‐resistance methyltransferase RlmA II
Author(s) -
Lebars Isabelle,
Yoshizawa Satoko,
Stenholm Anne R.,
Guittet Eric,
Douthwaite Stephen,
Fourmy Dominique
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg022
Subject(s) - 23s ribosomal rna , tylosin , biology , ribosomal rna , transfer rna , ribosome , methyltransferase , streptomyces fradiae , 50s , rna , stem loop , genetics , biochemistry , streptomyces , bacteria , dna , antibiotics , actinomycetales , methylation , gene
The bacterial rRNA methyltransferase RlmA II (formerly TlrB) contributes to resistance against tylosin‐like 16‐membered ring macrolide antibiotics. RlmA II was originally discovered in the tylosin‐producer Streptomyces fradiae , and members of this subclass of methyltransferases have subsequently been found in other Gram‐positive bacteria, including Streptococcus pneumoniae . In all cases, RlmA II methylates 23S rRNA at nucleotide G748, which is situated in a stem–loop (hairpin 35) at the macrolide binding site of the ribosome. The conformation of hairpin 35 recognized by RlmA II is shown here by NMR spectroscopy to resemble the anticodon loop of tRNA. The loop folds independently of the rest of the 23S rRNA, and is stabilized by a non‐canonical G–A pair and a U‐turn motif, rendering G748 accessible. Binding of S.pneumoniae RlmA II induces changes in NMR signals at specific nucleotides that are involved in the methyltransferase–RNA interaction. The conformation of hairpin 35 that interacts with RlmA II is radically different from the structure this hairpin adopts within the 50S subunit. This indicates that the hairpin undergoes major structural rearrangement upon interaction with ribosomal proteins during 50S assembly.