6r25: Difference between revisions
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==Structure of LSD2/NPAC-linker/nucleosome core particle complex: Class 3== | |||
<StructureSection load='6r25' size='340' side='right'caption='[[6r25]], [[Resolution|resolution]] 4.61Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6r25]] is a 13 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R25 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R25 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=6r25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r25 OCA], [http://pdbe.org/6r25 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r25 RCSB], [http://www.ebi.ac.uk/pdbsum/6r25 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r25 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). | |||
<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> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6r25" 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 3
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