A structural basis for streptomycin-induced misreading of the genetic code

During protein synthesis, the ribosome selects aminoacyl-tRNAs with anticodons matching the mRNA codon present in the A-site of the small ribosomal subunit. The aminoglycoside antibiotic streptomycin disrupts decoding by binding close to the site of codon recognition. Here we use X-ray crystallography to define the impact of streptomycin on the decoding site of the Thermus thermophilus 30S ribosomal subunit in complexes with cognate or near-cognate anticodon stem-loop analogs (ASLs) and mRNA. Our crystal structures display a significant local distortion of 16S rRNA induced by streptomycin, including the crucial bases A1492 and A1493 that participate directly in codon recognition. Consistent with kinetic data, we observe that streptomycin stabilizes the near-cognate ASL complex, while destabilizing the cognate ASL complex. These data reveal how streptomycin disrupts the recognition of cognate ASLs and yet improves recognition of a near-cognate ASL.