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| | ==Crystal Structure of full length PRMT5/MEP50 complexes from Xenopus laevis== | | ==Crystal Structure of full length PRMT5/MEP50 complexes from Xenopus laevis== |
| - | <StructureSection load='4g56' size='340' side='right' caption='[[4g56]], [[Resolution|resolution]] 2.95Å' scene=''> | + | <StructureSection load='4g56' size='340' side='right'caption='[[4g56]], [[Resolution|resolution]] 2.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4g56]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G56 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G56 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4g56]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G56 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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]] 2.95Å</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> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hsl7, PRMT5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 Xenopus laevis]), MEP50, MGC81050, wdr77 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 Xenopus laevis])</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=4g56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g56 OCA], [https://pdbe.org/4g56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g56 RCSB], [https://www.ebi.ac.uk/pdbsum/4g56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g56 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4g56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g56 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4g56 RCSB], [http://www.ebi.ac.uk/pdbsum/4g56 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ANM5_XENLA ANM5_XENLA]] Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA. Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins; such methylation being required for the assembly and biogenesis of snRNP core particles. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation (By similarity). Methylates the arginine in the motif G-R-G-X-G in its substrates histone H2A, H2AFX and H4, producing both monomethylated and symmetrically dimethylated 'Arg-3'. Methylates nucleoplasmin at 'Arg-192', producing both monomethylated and symmetrically dimethylated 'Arg-192'. Involved in the DNA replication checkpoint. Promotes entry into mitosis by promoting the proteasomal degradation of wee2-a. [[http://www.uniprot.org/uniprot/MEP50_XENLA MEP50_XENLA]] Non-catalytic component of the 20S prmt5-containing methyltransferase complex, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins and histones. Required for normal prmt5 methyltransferase activity. | + | [https://www.uniprot.org/uniprot/ANM5_XENLA ANM5_XENLA] Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA. Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins; such methylation being required for the assembly and biogenesis of snRNP core particles. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation (By similarity). Methylates the arginine in the motif G-R-G-X-G in its substrates histone H2A, H2AFX and H4, producing both monomethylated and symmetrically dimethylated 'Arg-3'. Methylates nucleoplasmin at 'Arg-192', producing both monomethylated and symmetrically dimethylated 'Arg-192'. Involved in the DNA replication checkpoint. Promotes entry into mitosis by promoting the proteasomal degradation of wee2-a. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4g56" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Xenopus laevis]] | | [[Category: Xenopus laevis]] |
| - | [[Category: Almo, S C]] | + | [[Category: Almo SC]] |
| - | [[Category: Bonanno, J]] | + | [[Category: Bonanno J]] |
| - | [[Category: Ho, M]] | + | [[Category: Ho M]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Shechter D]] |
| - | [[Category: Shechter, D]] | + | [[Category: Wilczek C]] |
| - | [[Category: Wilczek, C]] | + | |
| - | [[Category: Histone methylation]]
| + | |
| - | [[Category: Protein arginine methyltransferase]]
| + | |
| - | [[Category: Protein complex]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
ANM5_XENLA Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA. Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins; such methylation being required for the assembly and biogenesis of snRNP core particles. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation (By similarity). Methylates the arginine in the motif G-R-G-X-G in its substrates histone H2A, H2AFX and H4, producing both monomethylated and symmetrically dimethylated 'Arg-3'. Methylates nucleoplasmin at 'Arg-192', producing both monomethylated and symmetrically dimethylated 'Arg-192'. Involved in the DNA replication checkpoint. Promotes entry into mitosis by promoting the proteasomal degradation of wee2-a.
Publication Abstract from PubMed
The arginine methyltransferase PRMT5-MEP50 is required for embryogenesis and is misregulated in many cancers. PRMT5 targets a wide variety of substrates, including histone proteins involved in specifying an epigenetic code. However, the mechanism by which PRMT5 utilizes MEP50 to discriminate substrates and to specifically methylate target arginines is unclear. To test a model in which MEP50 is critical for substrate recognition and orientation, we determined the crystal structure of Xenopus laevis PRMT5-MEP50 complexed with S-adenosylhomocysteine (SAH). PRMT5-MEP50 forms an unusual tetramer of heterodimers with substantial surface negative charge. MEP50 is required for PRMT5-catalyzed histone H2A and H4 methyltransferase activity and binds substrates independently. The PRMT5 catalytic site is oriented towards the cross-dimer paired MEP50. Histone peptide arrays and solution assays demonstrate that PRMT5-MEP50 activity is inhibited by substrate phosphorylation and enhanced by substrate acetylation. Electron microscopy and reconstruction showed substrate centered on MEP50. These data support a mechanism in which MEP50 binds substrate and stimulates PRMT5 activity modulated by substrate post-translational modifications.
Structure of the Arginine Methyltransferase PRMT5-MEP50 Reveals a Mechanism for Substrate Specificity.,Ho MC, Wilczek C, Bonanno JB, Xing L, Seznec J, Matsui T, Carter LG, Onikubo T, Kumar PR, Chan MK, Brenowitz M, Cheng RH, Reimer U, Almo SC, Shechter D PLoS One. 2013;8(2):e57008. doi: 10.1371/journal.pone.0057008. Epub 2013 Feb 25. PMID:23451136[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ho MC, Wilczek C, Bonanno JB, Xing L, Seznec J, Matsui T, Carter LG, Onikubo T, Kumar PR, Chan MK, Brenowitz M, Cheng RH, Reimer U, Almo SC, Shechter D. Structure of the Arginine Methyltransferase PRMT5-MEP50 Reveals a Mechanism for Substrate Specificity. PLoS One. 2013;8(2):e57008. doi: 10.1371/journal.pone.0057008. Epub 2013 Feb 25. PMID:23451136 doi:10.1371/journal.pone.0057008
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