Human ribosomes interactions reveal the binding landscape of neomycin

Cryo-EM shows neomycin binds extensively at multiple sites on both human mitochondrial and cytosolic ribosomes in vitro, including conserved decoding-center regions.

• Why it matters: The toxicity model assumes aminoglycosides mainly inhibit mitoribosomes, but it is unclear how structural binding relates to what is recovered after cellular exposure.
• What they did: The study combined Cryo-EM with functional assays, mapping neomycin occupancy on purified human ribosomes and comparing it to ribosomes isolated from neomycin-treated cells.
• The result: After cellular exposure, mitoribosomes show no detectable neomycin density and cytosolic sites show reduced occupancy, yet neomycin still induces widespread stop-codon readthrough with minimal effects on global mitochondrial and cytosolic protein synthesis.

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