4a8j: Difference between revisions

Revision as of 10:48, 9 May 2024

Crystal Structure of the Elongator subcomplex Elp456

Structural highlights

4a8j is a 6 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:	MSE
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ELP6_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. ELP6 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]

Publication Abstract from PubMed

Elongator was initially described as an RNA polymerase II-associated factor but has since been associated with a broad range of cellular activities. It has also attracted clinical attention because of its role in certain neurodegenerative diseases. Here we describe the crystal structure of the Saccharomyces cerevisiae subcomplex of Elongator proteins 4, 5 and 6 (Elp456). The subunits each show almost identical RecA folds that form a heterohexameric ring-like structure resembling hexameric RecA-like ATPases. This structural finding is supported by different complementary in vitro and in vivo approaches, including the specific binding of the hexameric Elp456 subcomplex to tRNAs in a manner regulated by ATP. Our results support a role of Elongator in tRNA modification, explain the importance of each of the Elp4, Elp5 and Elp6 subunits for complex integrity and suggest a model for the overall architecture of the holo-Elongator complex.

The Elongator subcomplex Elp456 is a hexameric RecA-like ATPase.,Glatt S, Letoquart J, Faux C, Taylor NM, Seraphin B, Muller CW Nat Struct Mol Biol. 2012 Feb 19;19(3):314-20. doi: 10.1038/nsmb.2234. PMID:22343726^[7]

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
↑ 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
↑ Glatt S, Letoquart J, Faux C, Taylor NM, Seraphin B, Muller CW. The Elongator subcomplex Elp456 is a hexameric RecA-like ATPase. Nat Struct Mol Biol. 2012 Feb 19;19(3):314-20. doi: 10.1038/nsmb.2234. PMID:22343726 doi:10.1038/nsmb.2234

Proteopedia Page Contributors and Editors (what is this?)

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] 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

[7] Glatt S, Letoquart J, Faux C, Taylor NM, Seraphin B, Muller CW. The Elongator subcomplex Elp456 is a hexameric RecA-like ATPase. Nat Struct Mol Biol. 2012 Feb 19;19(3):314-20. doi: 10.1038/nsmb.2234. PMID:22343726 doi:10.1038/nsmb.2234

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[2]

[3]

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[6]

[7]

@@ Line 3: / Line 3: @@
 <StructureSection load='4a8j' size='340' side='right'caption='[[4a8j]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4a8j]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A8J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A8J FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4a8j]] is a 6 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=4A8J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A8J FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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]] 2.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=4a8j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a8j OCA], [https://pdbe.org/4a8j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a8j RCSB], [https://www.ebi.ac.uk/pdbsum/4a8j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a8j ProSAT]</span></td></tr>
 </table>
 == 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/ELP6_YEAST ELP6_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. ELP6 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:15769872</ref>  [[https://www.uniprot.org/uniprot/ELP5_YEAST ELP5_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. IKI1 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:15769872</ref>
+[https://www.uniprot.org/uniprot/ELP6_YEAST ELP6_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. ELP6 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:15769872</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Baker's yeast]]
 [[Category: Large Structures]]
-[[Category: Glatt, S]]
+[[Category: Saccharomyces cerevisiae S288C]]
-[[Category: Mueller, C W]]
+[[Category: Glatt S]]
-[[Category: Transcription]]
+[[Category: Mueller CW]]

4a8j: Difference between revisions

Revision as of 10:48, 9 May 2024

Crystal Structure of the Elongator subcomplex Elp456

Structural highlights

Function

Publication Abstract from PubMed

References

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