2ri3

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the 3-MBT repeats from human L3MBTL1 with N358Q point mutation

Structural highlights

2ri3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LMBL1_HUMAN Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Human L3MBTL1, which contains three malignant brain tumor (MBT) repeats, binds monomethylated and dimethylated lysines, but not trimethylated lysines, in several histone sequence contexts. In crystal structures of L3MBTL1 complexes, the monomethyl- and dimethyllysines insert into a narrow and deep cavity of aromatic residue-lined pocket 2, while a proline ring inserts into shallower pocket 1. We have also engineered a single Y to E substitution within the aromatic cage of the BPTF PHD finger, resulting in a reversal of binding preference from trimethyl- to dimethyllysine in an H3K4 sequence context. In both the "cavity insertion" (L3MBTL1) and "surface groove" (PHD finger) modes of methyllysine recognition, a carboxylate group both hydrogen bonds and ion pairs to the methylammonium proton. Our structural and binding studies of these two modules provide insights into the molecular principles governing the decoding of lysine methylation states, thereby highlighting a methylation state-specific layer of histone mark readout impacting on epigenetic regulation.

Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger.,Li H, Fischle W, Wang W, Duncan EM, Liang L, Murakami-Ishibe S, Allis CD, Patel DJ Mol Cell. 2007 Nov 30;28(4):677-91. PMID:18042461^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Trojer P, Li G, Sims RJ 3rd, Vaquero A, Kalakonda N, Boccuni P, Lee D, Erdjument-Bromage H, Tempst P, Nimer SD, Wang YH, Reinberg D. L3MBTL1, a histone-methylation-dependent chromatin lock. Cell. 2007 Jun 1;129(5):915-28. PMID:17540172 doi:10.1016/j.cell.2007.03.048
↑ Kalakonda N, Fischle W, Boccuni P, Gurvich N, Hoya-Arias R, Zhao X, Miyata Y, Macgrogan D, Zhang J, Sims JK, Rice JC, Nimer SD. Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1. Oncogene. 2008 Jul 17;27(31):4293-304. doi: 10.1038/onc.2008.67. Epub 2008 Apr, 14. PMID:18408754 doi:10.1038/onc.2008.67
↑ Saddic LA, West LE, Aslanian A, Yates JR 3rd, Rubin SM, Gozani O, Sage J. Methylation of the retinoblastoma tumor suppressor by SMYD2. J Biol Chem. 2010 Nov 26;285(48):37733-40. doi: 10.1074/jbc.M110.137612. Epub, 2010 Sep 24. PMID:20870719 doi:10.1074/jbc.M110.137612
↑ West LE, Roy S, Lachmi-Weiner K, Hayashi R, Shi X, Appella E, Kutateladze TG, Gozani O. The MBT repeats of L3MBTL1 link set8 mediated p53 methylation at lysine 382 to target gene repression. J Biol Chem. 2010 Sep 24. PMID:20870725 doi:10.1074/jbc.M110.139527
↑ Li H, Fischle W, Wang W, Duncan EM, Liang L, Murakami-Ishibe S, Allis CD, Patel DJ. Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger. Mol Cell. 2007 Nov 30;28(4):677-91. PMID:18042461 doi:10.1016/j.molcel.2007.10.023

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ri3"

Categories: Homo sapiens | Large Structures | Li H | Patel DJ

@@ Line 3: / Line 3: @@
 <StructureSection load='2ri3' size='340' side='right'caption='[[2ri3]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ri3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RI3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ri3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RI3 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CML:(2S)-2-{[(2R)-2-AMINO-2-CARBOXYETHYL]SULFANYL}BUTANEDIOIC+ACID'>CML</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CML:(2S)-2-{[(2R)-2-AMINO-2-CARBOXYETHYL]SULFANYL}BUTANEDIOIC+ACID'>CML</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2rhi|2rhi]], [[2rhu|2rhu]], [[2rhx|2rhx]], [[2rhy|2rhy]], [[2rhz|2rhz]], [[2ri2|2ri2]], [[2ri5|2ri5]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">L3MBTL, KIAA0681, L3MBT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2ri3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ri3 OCA], [https://pdbe.org/2ri3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ri3 RCSB], [https://www.ebi.ac.uk/pdbsum/2ri3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ri3 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/LMBL1_HUMAN LMBL1_HUMAN]] Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.<ref>PMID:17540172</ref> <ref>PMID:18408754</ref> <ref>PMID:20870719</ref> <ref>PMID:20870725</ref>
+[https://www.uniprot.org/uniprot/LMBL1_HUMAN LMBL1_HUMAN] Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.<ref>PMID:17540172</ref> <ref>PMID:18408754</ref> <ref>PMID:20870719</ref> <ref>PMID:20870725</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 35: / Line 33: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Li, H]]
+[[Category: Li H]]
-[[Category: Patel, D J]]
+[[Category: Patel DJ]]
-[[Category: Alternative splicing]]
-[[Category: Beta barrel]]
-[[Category: Chromatin regulator]]
-[[Category: Dna-binding]]
-[[Category: Metal-binding]]
-[[Category: Nucleus]]
-[[Category: Repressor]]
-[[Category: Transcription]]
-[[Category: Transcription regulation]]
-[[Category: Zinc]]
-[[Category: Zinc-finger]]

2ri3

From Proteopedia

Current revision

Crystal structure of the 3-MBT repeats from human L3MBTL1 with N358Q point mutation

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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