|
|
| Line 4: |
Line 4: |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[4ejs]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EJS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EJS FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4ejs]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EJS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EJS FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ejs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejs OCA], [https://pdbe.org/4ejs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ejs RCSB], [https://www.ebi.ac.uk/pdbsum/4ejs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejs ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.606Å</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ejs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ejs OCA], [https://pdbe.org/4ejs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ejs RCSB], [https://www.ebi.ac.uk/pdbsum/4ejs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ejs ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ELP4_YEAST 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.<ref>PMID:10024884</ref> <ref>PMID:11296232</ref> <ref>PMID:11689709</ref> <ref>PMID:11904415</ref> <ref>PMID:13680368</ref> <ref>PMID:15138274</ref> <ref>PMID:15769872</ref>
| + | [https://www.uniprot.org/uniprot/ELP4_YEAST 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.<ref>PMID:10024884</ref> <ref>PMID:11296232</ref> <ref>PMID:11689709</ref> <ref>PMID:11904415</ref> <ref>PMID:13680368</ref> <ref>PMID:15138274</ref> <ref>PMID:15769872</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Elongator is a multiprotein complex composed of two subcomplexes, Elp1-3 and Elp4-6. Elongator is highly conserved between yeast and humans and plays an important role in RNA polymerase II-mediated transcriptional elongation and many other processes, including cytoskeleton organization, exocytosis, and tRNA modification. Here, we determined the crystal structure of the Elp4-6 subcomplex of yeast. The overall structure of Elp4-6 revealed that Elp6 acts as a bridge to assemble Elp4 and Elp5. Detailed structural and sequence analyses revealed that each subunit in the Elp4-6 subcomplex forms a RecA-ATPase-like fold, although it lacks the key sequence signature of ATPases. Site-directed mutagenesis and biochemical analyses indicated that the Elp4-6 subcomplex can assemble into a hexameric ring-shaped structure in vitro and in vivo. Furthermore, GST pulldown assays showed that the ring-shaped assembly of the Elp4-6 subcomplex is important for its specific histone H3 binding. Our results may shed light on the substrate recognition and assembly of the holo-Elongator complex.
| + | |
| - | | + | |
| - | Crystal structure of elongator subcomplex Elp4-6.,Lin Z, Zhao W, Diao W, Xie X, Wang Z, Zhang J, Shen Y, Long J J Biol Chem. 2012 Jun 15;287(25):21501-8. Epub 2012 May 2. PMID:22556426<ref>PMID:22556426</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4ejs" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Structural highlights
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]
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
|
