Cryo-EM structures of the human Elongator complex at work

ABSTRACT: The deposited data concern the mapping of acetylation sites on wild-type and the K280A, Y363A mutants of Elp3 by LC-MS/MS. Abstract of the manuscript: 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 cycle. The structures at resolutions of up to 2.9 A 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 (ACO) 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 first high-resolution view of human Elongator and reveal its detailed mechanism of action.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Sebastian Glatt  

PROVIDER: MSV000092998 | MassIVE |

REPOSITORIES: MassIVE