8at6
From Proteopedia
Cryo-EM structure of yeast Elp456 subcomplex
Structural highlights
FunctionELP4_YEAST Acts as component of the RNA polymerase II elongator complex, which is a major histone acetyltransferase component of the RNA polymerase II (RNAPII) holoenzyme and is involved in transcriptional elongation. Association with elongating RNAPII requires a hyperphosphorylated state of the RNAPII C-terminal domain (CTD). Elongator binds to both naked and nucleosomal DNA, can acetylate both core and nucleosomal histones, and is involved in chromatin remodeling. It acetylates histones H3, preferentially at 'Lys-14', and H4, preferentially at 'Lys-8'. It functions as a gamma-toxin target (TOT); disruption of the complex confers resistance to Kluyveromyces lactis toxin zymocin (pGKL1 killer toxin). May also be involved in sensitiviy to Pichia inositovora toxin. May be involved in tRNA modification. ELP4 is required for the complex integrity and the complex HAT activity but is not required for the association of the complex with nascent RNA transcript. Is required for an early step in synthesis of 5-methoxycarbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) groups present on uridines at the wobble position in tRNA.[1] [2] [3] [4] [5] [6] [7] 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[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Large Structures | Saccharomyces cerevisiae | Abbassi N | Biela A | Chramiec-Glabik A | Dobosz D | Gaik M | Glatt S | Hammermeister A | Indyka P | Jaciuk M | Kaszuba K | Koscielniak A | Kosinski J | Krutyholowa R | Lin T-Y | Rawski M | Schaffrath R | Scherf D
