Abstract of the PDB Structure's related Publication:
The highly conserved Elongator complex modifies transfer RNAs (tRNAs) in their wobble base position, thereby regulating protein synthesis and ensuring proteome stability. The precise mechanisms of tRNA recognition and its modification reaction remain elusive. Here, we show cryo-electron microscopy structures of the catalytic subcomplex of Elongator and its tRNA-bound state at resolutions of 3.3 and 4.4 Å. The structures resolve details of the catalytic site, including the substrate tRNA, the iron-sulfur cluster, and a SAM molecule, which are all validated by mutational analyses in vitro and in vivo. tRNA binding induces conformational rearrangements, which precisely position the targeted anticodon base in the active site. Our results provide the molecular basis for substrate recognition of Elongator, essential to understand its cellular function and role in neurodegenerative diseases and cancer.
One of the six protein cofactors required for the synthesis of 5-carboxymethyl group (cm5) on the wobble uridine-34 of a few tRNA. Acetate or acetyl-CoA is the donor of acetyl group, but the detailed mechanism of the reaction is still unknown. The cm5U derivative is the intermediate for further biochemical transformation of U34 derivative to either 5-methoxycarbonylmethyl uridine (mcm5U) catalysed by Trm9/Trm112 or 5-carbamoylmethyluridine (ncm5U) catalysed by a still unknown enzyme. Mutation in Elp (especially Elp3) influences telomeric gene silencing and DNA damage response. The multi-subunit complex El1-6 also interacts with elongating RNA polymerase II (RNAPII) is thought to facilitate transcription through histone acetylation.