SNAP output for PDB entry 8ptx [SNAP web server]

PDB-id

8ptx; SNAP-derived features in text and JSON formats; DNAproDB

Class

translation

Method

cryo-EM (2.87 Å)

Summary

cryo-EM structure of human elp123 in complex with trna, acetyl-coa, 5'-deoxyadenosine and methionine

Reference

Abbassi NE, Jaciuk M, Scherf D, Bohnert P, Rau A, Hammermeister A, Rawski M, Indyka P, Wazny G, Chramiec-Glabik A, Dobosz D, Skupien-Rabian B, Jankowska U, Rappsilber J, Schaffrath R, Lin TY, Glatt S (2024): "Cryo-EM structures of the human Elongator complex at work." Nat Commun, 15, 4094. doi: 10.1038/s41467-024-48251-y.

Abstract

tRNA modifications affect ribosomal elongation speed and co-translational folding dynamics. The Elongator complex is responsible for introducing 5-carboxymethyl at wobble uridine bases (cm₅U₃₄) in eukaryotic tRNAs. However, the structure and function of human Elongator remain poorly understood. In this study, we present a series of cryo-EM structures of human ELP123 in complex with tRNA and cofactors at four different stages of the reaction. The structures at resolutions of up to 2.9 Å together with complementary functional analyses reveal the molecular mechanism of the modification reaction. Our results show that tRNA binding exposes a universally conserved uridine at position 33 (U₃₃), which triggers acetyl-CoA hydrolysis. We identify a series of conserved residues that are crucial for the radical-based acetylation of U₃₄ and profile the molecular effects of patient-derived mutations. Together, we provide the high-resolution view of human Elongator and reveal its detailed mechanism of action.