29IZ

Dormant 80S:eEF2:SERBP1:tRNA complex from human cells treated with toxin NT-2

This is a non-PDB format compatible entry.

Summary for 29IZ

• Entry DOI: 10.2210/pdb29iz/pdb
• EMDB information: 57204
• Descriptor: Large ribosomal subunit protein uL30, 60S ribosomal protein L17, 60S ribosomal protein L18, ... (90 entities in total)
• Functional Keywords: toxin nt-2, translation inhibitor, mycotoxin, trichothecene, ribosome
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 82
• Total formula weight: 3958129.78

Authors

Rabl, J.,Karousis, E.D. (deposition date: 2026-03-16, release date: 2026-09-30, Last modification date: 2026-10-07)

Primary citation

Schwaller, N.,Andenmatten, D.,Luginbuhl, J.,Rabl, J.,Baur, H.,Chambon, M.,Vesin, J.,Turcatti, G.,Karousis, E.D.
A human cell-free translation screen identifies the NT-2 mycotoxin as a ribosomal inhibitor that binds the peptidyl transferase center.
Commun Biol, 9:-, 2026

PubMed Abstract: Translation inhibitors are invaluable for probing ribosome function and therapeutic applications, but systematic discovery in human systems is limited by the lack of scalable, screening-compatible cell-free platforms. Here, we establish a robust high-throughput screening using human lysates that bypasses cellular cytotoxic effects. After screening ~28,000 small molecules, we identified known and a novel translation inhibitor, including NT-2, a trichothecene mycotoxin produced by the pathogenic Fusarium sporotrichioides. NT-2 suppressed protein synthesis in human cells and yeast lysates, while sparing translation in bacteria and intact yeast cells. Cryo-EM at 1.76 Å revealed NT-2 bound at the peptidyl transferase center of the human 60S ribosome. In addition, cryoEM classification of NT-2 treated cells shows ribosomes in an inactive eEF2/SERBP1-bound dormant state. Together, these results expose NT-2 as a previously unrecognized environmental inhibitor of mammalian protein synthesis and demonstrate the power of cell-free translation screening to reveal new inhibitors with unexpected ribosome fates.

PubMed: 42778572
DOI: 10.1038/s42003-026-10743-6

Experimental method

ELECTRON MICROSCOPY (2.08 Å)