Details

Autor(en) / Beteiligte

• Yokoyama, Shigeyuki
• Fucini, Paola
• Schluenzen, Frank
• Takemoto, Chie
• Wilson, Daniel N
• Kaminishi, Tatsuya
• Harms, Joerg M
• Hanawa-Suetsugu, Kyoko
• Szaflarski, Witold
• Kawazoe, Masahito
• Shirouzu, Mikako
• Nierhaus, Knud H

Titel

The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding and inhibit canonical translation initiation

Ist Teil von

• Nature structural & molecular biology, 2006-10, Vol.13 (10), p.871-878

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• Kasugamycin (Ksg) specifically inhibits translation initiation of canonical but not of leaderless messenger RNAs. Ksg inhibition is thought to occur by direct competition with initiator transfer RNA. The 3.35-A structure of Ksg bound to the 30S ribosomal subunit presented here provides a structural description of two Ksg-binding sites as well as a basis for understanding Ksg resistance. Notably, neither binding position overlaps with P-site tRNA; instead, Ksg mimics codon nucleotides at the P and E sites by binding within the path of the mRNA. Coupled with biochemical experiments, our results suggest that Ksg indirectly inhibits P-site tRNA binding through perturbation of the mRNA-tRNA codon-anticodon interaction during 30S canonical initiation. In contrast, for 70S-type initiation on leaderless mRNA, the overlap between mRNA and Ksg is reduced and the binding of tRNA is further stabilized by the presence of the 50S subunit, minimizing Ksg efficacy.