8at6 | pdb_00008at6

Cryo-EM structure of yeast Elp456 subcomplex

Structural highlights

8at6 is a 6 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.7Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ELP4_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 PubMed

Transfer 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

↑ Otero G, Fellows J, Li Y, de Bizemont T, Dirac AM, Gustafsson CM, Erdjument-Bromage H, Tempst P, Svejstrup JQ. Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. Mol Cell. 1999 Jan;3(1):109-18. PMID:10024884
↑ Frohloff F, Fichtner L, Jablonowski D, Breunig KD, Schaffrath R. Saccharomyces cerevisiae Elongator mutations confer resistance to the Kluyveromyces lactis zymocin. EMBO J. 2001 Apr 17;20(8):1993-2003. PMID:11296232 doi:10.1093/emboj/20.8.1993
↑ Krogan NJ, Greenblatt JF. Characterization of a six-subunit holo-elongator complex required for the regulated expression of a group of genes in Saccharomyces cerevisiae. Mol Cell Biol. 2001 Dec;21(23):8203-12. PMID:11689709 doi:10.1128/MCB.21.23.8203-8212.2001
↑ Winkler GS, Kristjuhan A, Erdjument-Bromage H, Tempst P, Svejstrup JQ. Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivo. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3517-22. PMID:11904415 doi:10.1073/pnas.022042899
↑ Klassen R, Meinhardt F. Structural and functional analysis of the killer element pPin1-3 from Pichia inositovora. Mol Genet Genomics. 2003 Nov;270(2):190-9. Epub 2003 Sep 9. PMID:13680368 doi:10.1007/s00438-003-0920-5
↑ Petrakis TG, Wittschieben BO, Svejstrup JQ. Molecular architecture, structure-function relationship, and importance of the Elp3 subunit for the RNA binding of holo-elongator. J Biol Chem. 2004 Jul 30;279(31):32087-92. Epub 2004 May 11. PMID:15138274 doi:10.1074/jbc.M403361200
↑ Huang B, Johansson MJ, Bystrom AS. An early step in wobble uridine tRNA modification requires the Elongator complex. RNA. 2005 Apr;11(4):424-36. PMID:15769872 doi:11/4/424
↑ Jaciuk M, Scherf D, Kaszuba K, Gaik M, Rau A, Kościelniak A, Krutyhołowa R, Rawski M, Indyka P, Graziadei A, Chramiec-Głąbik A, Biela A, Dobosz D, Lin TY, Abbassi NE, Hammermeister A, Rappsilber J, Kosinski J, Schaffrath R, Glatt S. Cryo-EM structure of the fully assembled Elongator complex. Nucleic Acids Res. 2023 Mar 21;51(5):2011-2032. PMID:36617428 doi:10.1093/nar/gkac1232

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OCA

[1] Otero G, Fellows J, Li Y, de Bizemont T, Dirac AM, Gustafsson CM, Erdjument-Bromage H, Tempst P, Svejstrup JQ. Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. Mol Cell. 1999 Jan;3(1):109-18. PMID:10024884

[2] Frohloff F, Fichtner L, Jablonowski D, Breunig KD, Schaffrath R. Saccharomyces cerevisiae Elongator mutations confer resistance to the Kluyveromyces lactis zymocin. EMBO J. 2001 Apr 17;20(8):1993-2003. PMID:11296232 doi:10.1093/emboj/20.8.1993

[3] Krogan NJ, Greenblatt JF. Characterization of a six-subunit holo-elongator complex required for the regulated expression of a group of genes in Saccharomyces cerevisiae. Mol Cell Biol. 2001 Dec;21(23):8203-12. PMID:11689709 doi:10.1128/MCB.21.23.8203-8212.2001

[4] Winkler GS, Kristjuhan A, Erdjument-Bromage H, Tempst P, Svejstrup JQ. Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivo. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3517-22. PMID:11904415 doi:10.1073/pnas.022042899

[5] Klassen R, Meinhardt F. Structural and functional analysis of the killer element pPin1-3 from Pichia inositovora. Mol Genet Genomics. 2003 Nov;270(2):190-9. Epub 2003 Sep 9. PMID:13680368 doi:10.1007/s00438-003-0920-5

[6] Petrakis TG, Wittschieben BO, Svejstrup JQ. Molecular architecture, structure-function relationship, and importance of the Elp3 subunit for the RNA binding of holo-elongator. J Biol Chem. 2004 Jul 30;279(31):32087-92. Epub 2004 May 11. PMID:15138274 doi:10.1074/jbc.M403361200

[7] Huang B, Johansson MJ, Bystrom AS. An early step in wobble uridine tRNA modification requires the Elongator complex. RNA. 2005 Apr;11(4):424-36. PMID:15769872 doi:11/4/424

[8] Jaciuk M, Scherf D, Kaszuba K, Gaik M, Rau A, Kościelniak A, Krutyhołowa R, Rawski M, Indyka P, Graziadei A, Chramiec-Głąbik A, Biela A, Dobosz D, Lin TY, Abbassi NE, Hammermeister A, Rappsilber J, Kosinski J, Schaffrath R, Glatt S. Cryo-EM structure of the fully assembled Elongator complex. Nucleic Acids Res. 2023 Mar 21;51(5):2011-2032. PMID:36617428 doi:10.1093/nar/gkac1232

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8at6 | pdb_00008at6

Cryo-EM structure of yeast Elp456 subcomplex

Structural highlights

Function

Publication Abstract from PubMed

References

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