6r1u
From Proteopedia
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- | '''Unreleased structure''' | ||
- | + | ==Structure of LSD2/NPAC-linker/nucleosome core particle complex: Class 2== | |
+ | <StructureSection load='6r1u' size='340' side='right'caption='[[6r1u]], [[Resolution|resolution]] 4.36Å' scene=''> | ||
+ | == Structural highlights == | ||
+ | <table><tr><td colspan='2'>[[6r1u]] is a 13 chain structure. 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> | ||
+ | </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> | ||
+ | <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> | ||
+ | </table> | ||
+ | == Function == | ||
+ | [[http://www.uniprot.org/uniprot/KDM1B_HUMAN 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). [[http://www.uniprot.org/uniprot/H4_XENLA 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. [[http://www.uniprot.org/uniprot/GLYR1_HUMAN 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).<ref>PMID:16352664</ref> <ref>PMID:20850016</ref> [[http://www.uniprot.org/uniprot/H32_XENLA 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. [[http://www.uniprot.org/uniprot/H2B11_XENLA 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. | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == 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<ref>PMID:30970244</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | + | </div> | |
- | [[Category: | + | <div class="pdbe-citations 6r1u" style="background-color:#fffaf0;"></div> |
+ | == References == | ||
+ | <references/> | ||
+ | __TOC__ | ||
+ | </StructureSection> | ||
+ | [[Category: Large Structures]] | ||
[[Category: Chittori, S]] | [[Category: Chittori, S]] | ||
[[Category: Marabelli, C]] | [[Category: Marabelli, C]] | ||
[[Category: Mattevi, A]] | [[Category: Mattevi, A]] | ||
[[Category: Pilotto, S]] | [[Category: Pilotto, S]] | ||
+ | [[Category: Subramaniam, S]] | ||
+ | [[Category: Chromatin reader]] | ||
+ | [[Category: Epigenetic]] | ||
+ | [[Category: Evolution of protein function]] | ||
+ | [[Category: Flavoenzyme]] | ||
+ | [[Category: Gene regulation]] | ||
+ | [[Category: Histone demethylation]] | ||
+ | [[Category: Molecular recognition]] |
Revision as of 07:13, 24 April 2019
Structure of LSD2/NPAC-linker/nucleosome core particle complex: Class 2
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