A human cell-free translation screen identifies the NT-2 mycotoxin as a ribosomal inhibitor that binds the peptidyl transferase center.

A human cell-free translation screen identified NT-2 as a novel ribosomal inhibitor binding the peptidyl transferase center, disrupting mammalian protein synthesis.

• Why it matters: Understanding translation inhibitors is crucial for probing ribosome function and developing therapeutics, but current methods lack scalable, human-specific screening platforms, limiting discovery.
• What they did: Researchers developed a high-throughput human lysate-based screening of approximately 28,000 small molecules, leading to the identification of NT-2, a mycotoxin that inhibits translation in human and yeast systems.
• The result: NT-2 binds at the ribosome’s peptidyl transferase center, inducing an inactive ribosomal state, revealing environmental inhibitors of mammalian translation and demonstrating the screening platform’s potential to uncover unexpected ribosome interactions.