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- PDB-6r1u: Structure of LSD2/NPAC-linker/nucleosome core particle complex: C... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6r1u | ||||||
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Title | Structure of LSD2/NPAC-linker/nucleosome core particle complex: Class 2 | ||||||
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![]() | GENE REGULATION / Histone demethylation / chromatin reader / flavoenzyme / epigenetics / evolution of protein function / molecular recognition. | ||||||
Function / homology | ![]() epigenetic programing of female pronucleus / chromatin-protein adaptor activity / genomic imprinting / [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase / FAD-dependent H3K4me/H3K4me3 demethylase activity / transcription elongation-coupled chromatin remodeling / histone demethylase activity / nucleosome binding / transcription initiation-coupled chromatin remodeling / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux ...epigenetic programing of female pronucleus / chromatin-protein adaptor activity / genomic imprinting / [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase / FAD-dependent H3K4me/H3K4me3 demethylase activity / transcription elongation-coupled chromatin remodeling / histone demethylase activity / nucleosome binding / transcription initiation-coupled chromatin remodeling / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / methylated histone binding / FAD binding / HDMs demethylate histones / structural constituent of chromatin / UCH proteinases / NAD binding / nucleosome / nucleosome assembly / NADP binding / flavin adenine dinucleotide binding / histone binding / oxidoreductase activity / protein heterodimerization activity / chromatin binding / chromatin / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / DNA binding / zinc ion binding / nucleoplasm / nucleus / cytosol Similarity search - Function | ||||||
Biological species | ![]() ![]() synthetic construct (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.36 Å | ||||||
![]() | Marabelli, C. / Pilotto, S. / Chittori, S. / Subramaniam, S. / Mattevi, A. | ||||||
Funding support | ![]()
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![]() | ![]() Title: A Tail-Based Mechanism Drives Nucleosome Demethylation by the LSD2/NPAC Multimeric Complex. Authors: Chiara Marabelli / Biagina Marrocco / Simona Pilotto / Sagar Chittori / Sarah Picaud / Sara Marchese / Giuseppe Ciossani / Federico Forneris / Panagis Filippakopoulos / Guy Schoehn / Daniela ...Authors: Chiara Marabelli / Biagina Marrocco / Simona Pilotto / Sagar Chittori / Sarah Picaud / Sara Marchese / Giuseppe Ciossani / Federico Forneris / Panagis Filippakopoulos / Guy Schoehn / Daniela Rhodes / Sriram Subramaniam / Andrea Mattevi / ![]() ![]() ![]() ![]() ![]() ![]() Abstract: LSD1 and LSD2 are homologous histone demethylases with opposite biological outcomes related to chromatin silencing and transcription elongation, respectively. Unlike LSD1, LSD2 nucleosome-demethylase ...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. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 450.3 KB | Display | ![]() |
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PDB format | ![]() | 342.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 929 KB | Display | ![]() |
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Full document | ![]() | 970.9 KB | Display | |
Data in XML | ![]() | 53 KB | Display | |
Data in CIF | ![]() | 83.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4705MC ![]() 4704C ![]() 4710C ![]() 4711C ![]() 4712C ![]() 6r1tC ![]() 6r25C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 7 types, 11 molecules AEBFCGDHKLM
#1: Protein | Mass: 15303.930 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 11263.231 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Protein | Mass: 13978.241 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | Mass: 13524.752 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #7: Protein | | Mass: 87051.547 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #8: Protein | | Mass: 13528.271 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #9: Protein | | Mass: 15305.945 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-DNA chain , 2 types, 2 molecules IJ
#5: DNA chain | Mass: 45610.043 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#6: DNA chain | Mass: 45138.770 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-Non-polymers , 2 types, 4 molecules ![](data/chem/img/FAD.gif)
![](data/chem/img/ZN.gif)
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#10: Chemical | ChemComp-FAD / |
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#11: Chemical |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Value: 0.29 MDa / Experimental value: YES | ||||||||||||||||||||||||||||||||||||||||||
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.87 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: LSD2/NPAC(214-225)/nucleosome was monodisperse (gel filtration peak isolation and concentration in buffer described. | ||||||||||||||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 3.05 nm / Nominal defocus min: 0.7 nm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 8 sec. / Electron dose: 1.25 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2078 |
Image scans | Movie frames/image: 40 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||
Particle selection | Num. of particles selected: 490558 | |||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||
3D reconstruction | Resolution: 4.36 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 72315 / Symmetry type: POINT | |||||||||||||||||||||||||
Atomic model building |
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Atomic model building |
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