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6r1u

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Structure of LSD2/NPAC-linker/nucleosome core particle complex: Class 2

6r1u, resolution 4.36Å

Structural highlights

6r1u is a 13 chain structure with sequence from African clawed frog and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	hist1h2aj, LOC494591 (African clawed frog), KDM1B, AOF1, C6orf193, LSD2 (HUMAN), GLYR1, HIBDL, NP60 (HUMAN), XELAEV_18002543mg (African clawed frog)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KDM1B_HUMAN] Histone demethylase that demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor. Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated 'Lys-4' of histone H3. Has no effect on tri-methylated 'Lys-4', mono-, di- or tri-methylated 'Lys-9', mono-, di- or tri-methylated 'Lys-27', mono-, di- or tri-methylated 'Lys-36' of histone H3, or on mono-, di- or tri-methylated 'Lys-20' of histone H4 (By similarity). [H4_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [GLYR1_HUMAN] May have oxidoreductase activity. Regulates p38 MAP kinase activity by mediating stress activation of p38alpha/MAPK14 and specifically regulating MAPK14 signaling. Indirectly promotes phosphorylation of MAPK14 and activation of ATF2. The phosphorylation of MAPK14 requires upstream activity of MAP2K4 and MAP2K6. Recruited on chromatin, recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3).^[1] ^[2] [H32_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [H2B11_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.

Publication Abstract from PubMed

LSD1 and LSD2 are homologous histone demethylases with opposite biological outcomes related to chromatin silencing and transcription elongation, respectively. Unlike LSD1, LSD2 nucleosome-demethylase activity relies on a specific linker peptide from the multidomain protein NPAC. We used single-particle cryoelectron microscopy (cryo-EM), in combination with kinetic and mutational analysis, to analyze the mechanisms underlying the function of the human LSD2/NPAC-linker/nucleosome complex. Weak interactions between LSD2 and DNA enable multiple binding modes for the association of the demethylase to the nucleosome. The demethylase thereby captures mono- and dimethyl Lys4 of the H3 tail to afford histone demethylation. Our studies also establish that the dehydrogenase domain of NPAC serves as a catalytically inert oligomerization module. While LSD1/CoREST forms a nucleosome docking platform at silenced gene promoters, LSD2/NPAC is a multifunctional enzyme complex with flexible linkers, tailored for rapid chromatin modification, in conjunction with the advance of the RNA polymerase on actively transcribed genes.

A Tail-Based Mechanism Drives Nucleosome Demethylation by the LSD2/NPAC Multimeric Complex.,Marabelli C, Marrocco B, Pilotto S, Chittori S, Picaud S, Marchese S, Ciossani G, Forneris F, Filippakopoulos P, Schoehn G, Rhodes D, Subramaniam S, Mattevi A Cell Rep. 2019 Apr 9;27(2):387-399.e7. doi: 10.1016/j.celrep.2019.03.061. PMID:30970244^[3]

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

References

↑ Fu J, Yang Z, Wei J, Han J, Gu J. Nuclear protein NP60 regulates p38 MAPK activity. J Cell Sci. 2006 Jan 1;119(Pt 1):115-23. Epub 2005 Dec 13. PMID:16352664 doi:10.1242/jcs.02699
↑ Vermeulen M, Eberl HC, Matarese F, Marks H, Denissov S, Butter F, Lee KK, Olsen JV, Hyman AA, Stunnenberg HG, Mann M. Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell. 2010 Sep 17;142(6):967-80. doi: 10.1016/j.cell.2010.08.020. PMID:20850016 doi:10.1016/j.cell.2010.08.020
↑ Marabelli C, Marrocco B, Pilotto S, Chittori S, Picaud S, Marchese S, Ciossani G, Forneris F, Filippakopoulos P, Schoehn G, Rhodes D, Subramaniam S, Mattevi A. A Tail-Based Mechanism Drives Nucleosome Demethylation by the LSD2/NPAC Multimeric Complex. Cell Rep. 2019 Apr 9;27(2):387-399.e7. doi: 10.1016/j.celrep.2019.03.061. PMID:30970244 doi:http://dx.doi.org/10.1016/j.celrep.2019.03.061

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6r1u"

@@ Line 3: / Line 3: @@
 <SX load='6r1u' size='340' side='right' viewer='molstar' caption='[[6r1u]], [[Resolution|resolution]] 4.36&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6r1u]] is a 13 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R1U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R1U FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6r1u]] is a 13 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R1U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6R1U FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hist1h2aj, LOC494591 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog]), KDM1B, AOF1, C6orf193, LSD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GLYR1, HIBDL, NP60 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), XELAEV_18002543mg ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog])</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=6r1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r1u OCA], [http://pdbe.org/6r1u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r1u RCSB], [http://www.ebi.ac.uk/pdbsum/6r1u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r1u ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6r1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r1u OCA], [http://pdbe.org/6r1u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r1u RCSB], [http://www.ebi.ac.uk/pdbsum/6r1u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r1u ProSAT]</span></td></tr>
 </table>
 == Function ==

6r1u

From Proteopedia

Current revision

Structure of LSD2/NPAC-linker/nucleosome core particle complex: Class 2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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