Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026Targeted mass spectrometry directly identified GpU(2′,3′-cp), a two-nucleotide product released by Cas13b6 from tRNA in vitro. This gave us a chemically defined candidate for the signal connecting Cas13 to 2TMβ. 6/11 100
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026In cells, removing either the membrane-spanning region or β-barrel of 2TMβ strongly reduced toxicity. The predicted ligand-pocket mutations Y157A and Y197A each also restored viability, linking this pocket to the cellular response. 7/11 110
Luis E. Valentin-Alvarado @luisvalentin.bsky.social · 09/10/2026We then asked how the candidate messengers affect 2TMβ assembly. Mass photometry showed that synthetic 2′,3′-cUMP and GpU(2′,3′-cp) promoted larger assemblies of the purified, soluble β-barrel. Pocket mutations altered this response. 8/11 100
