6r25

From Proteopedia

(Difference between revisions)

Current revision

Structure of LSD2/NPAC-linker/nucleosome core particle complex: Class 3

6r25, resolution 4.61Å

Structural highlights

6r25 is a 13 chain structure with sequence from Homo sapiens, Xenopus laevis and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.61Å
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

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^[1]

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

References

↑ 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/6r25"

@@ Line 3: / Line 3: @@
 <SX load='6r25' size='340' side='right' viewer='molstar' caption='[[6r25]], [[Resolution|resolution]] 4.61&Aring;' 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>
+<table><tr><td colspan='2'>[[6r25]] is a 13 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. 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 [https://proteopedia.org/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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.61&#8491;</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>
+<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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6r25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r25 OCA], [https://pdbe.org/6r25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r25 RCSB], [https://www.ebi.ac.uk/pdbsum/6r25 PDBsum], [https://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).
+[https://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.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 27: @@
 __TOC__
 </SX>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Chittori, S]]
+[[Category: Synthetic construct]]
-[[Category: Marabelli, C]]
+[[Category: Xenopus laevis]]
-[[Category: Mattevi, A]]
+[[Category: Chittori S]]
-[[Category: Pilotto, S]]
+[[Category: Marabelli C]]
-[[Category: Subramaniam, S]]
+[[Category: Mattevi A]]
-[[Category: Chromatin reader]]
+[[Category: Pilotto S]]
-[[Category: Epigenetic]]
+[[Category: Subramaniam S]]
-[[Category: Evolution of protein function]]
-[[Category: Flavoenzyme]]
-[[Category: Gene regulation]]
-[[Category: Histone demethylation]]
-[[Category: Molecular recognition]]

6r25

From Proteopedia

Current revision

Structure of LSD2/NPAC-linker/nucleosome core particle complex: Class 3

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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