8avg | pdb_00008avg
Cryo-EM structure of mouse Elp123 with bound SAM
Structural highlights
FunctionELP1_MOUSE Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (By similarity). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (PubMed:23717213). Regulates the migration and branching of projection neurons in the developing cerebral cortex, through a process depending on alpha-tubulin acetylation (PubMed:22854966). ELP1 binds to tRNA, mediating interaction of the elongator complex with tRNA (By similarity). May act as a scaffold protein that assembles active IKK-MAP3K14 complexes (IKKA, IKKB and MAP3K14/NIK) (By similarity).[UniProtKB:O95163][UniProtKB:Q06706][1] Publication Abstract from PubMedTransfer RNA (tRNA) molecules are essential to decode messenger RNA codons during protein synthesis. All known tRNAs are heavily modified at multiple positions through post-transcriptional addition of chemical groups. Modifications in the tRNA anticodons are directly influencing ribosome decoding and dynamics during translation elongation and are crucial for maintaining proteome integrity. In eukaryotes, wobble uridines are modified by Elongator, a large and highly conserved macromolecular complex. Elongator consists of two subcomplexes, namely Elp123 containing the enzymatically active Elp3 subunit and the associated Elp456 hetero-hexamer. The structure of the fully assembled complex and the function of the Elp456 subcomplex have remained elusive. Here, we show the cryo-electron microscopy structure of yeast Elongator at an overall resolution of 4.3 A. We validate the obtained structure by complementary mutational analyses in vitro and in vivo. In addition, we determined various structures of the murine Elongator complex, including the fully assembled mouse Elongator complex at 5.9 A resolution. Our results confirm the structural conservation of Elongator and its intermediates among eukaryotes. Furthermore, we complement our analyses with the biochemical characterization of the assembled human Elongator. Our results provide the molecular basis for the assembly of Elongator and its tRNA modification activity in eukaryotes. Cryo-EM structure of the fully assembled Elongator complex.,Jaciuk M, Scherf D, Kaszuba K, Gaik M, Rau A, Koscielniak A, Krutyholowa R, Rawski M, Indyka P, Graziadei A, Chramiec-Glabik A, Biela A, Dobosz D, Lin TY, Abbassi NE, Hammermeister A, Rappsilber J, Kosinski J, Schaffrath R, Glatt S Nucleic Acids Res. 2023 Mar 21;51(5):2011-2032. doi: 10.1093/nar/gkac1232. PMID:36617428[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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