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 ribosomal inhibitor binding the peptidyl transferase center, revealing its role as an environmental toxin in mammalian protein synthesis.

• Why it matters: Understanding translation inhibitors is crucial for probing ribosome function and developing therapies, but current discovery methods lack scalable human system platforms.
• 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 produced by Fusarium sporotrichioides, which inhibits protein synthesis selectively in human and yeast lysates.
• The result: Cryo-EM at 1.76 Å showed NT-2 bound at the peptidyl transferase center, and classification revealed ribosomes in an inactive dormant state, highlighting NT-2 as a novel environmental inhibitor of mammalian translation.