[English] 日本語
Yorodumi- EMDB-4705: Structure of LSD2/NPAC-linker/nucleosome core particle complex: C... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4705 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of LSD2/NPAC-linker/nucleosome core particle complex: Class 2 | |||||||||
Map data | LSD/NPAC(214-225)/Nucleosome: Class 2 | |||||||||
Sample |
| |||||||||
Keywords | Histone demethylation / chromatin reader / flavoenzyme / epigenetics / evolution of protein function / molecular recognition. / GENE REGULATION | |||||||||
Function / homology | Function and homology information epigenetic programing of female pronucleus / genomic imprinting / [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase / FAD-dependent H3K4me/H3K4me3 demethylase activity / chromatin-protein adaptor activity / transcription elongation-coupled chromatin remodeling / histone demethylase activity / nucleosome binding / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / methylated histone binding ...epigenetic programing of female pronucleus / genomic imprinting / [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase / FAD-dependent H3K4me/H3K4me3 demethylase activity / chromatin-protein adaptor activity / transcription elongation-coupled chromatin remodeling / histone demethylase activity / nucleosome binding / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / methylated histone binding / FAD binding / transcription initiation-coupled chromatin remodeling / HDMs demethylate histones / structural constituent of chromatin / NAD binding / UCH proteinases / nucleosome / nucleosome assembly / NADP binding / flavin adenine dinucleotide binding / histone binding / oxidoreductase activity / chromatin remodeling / protein heterodimerization activity / chromatin binding / chromatin / DNA binding / zinc ion binding / nucleoplasm / nucleus / cytosol Similarity search - Function | |||||||||
Biological species | Xenopus laevis (African clawed frog) / synthetic construct (others) / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.36 Å | |||||||||
Authors | Marabelli C / Pilotto S | |||||||||
Funding support | Italy, 1 items
| |||||||||
Citation | Journal: Cell Rep / Year: 2019 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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4705.map.gz | 63.1 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-4705-v30.xml emd-4705.xml | 26.1 KB 26.1 KB | Display Display | EMDB header |
Images | emd_4705.png | 235.7 KB | ||
Filedesc metadata | emd-4705.cif.gz | 8.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4705 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4705 | HTTPS FTP |
-Validation report
Summary document | emd_4705_validation.pdf.gz | 210 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_4705_full_validation.pdf.gz | 209.2 KB | Display | |
Data in XML | emd_4705_validation.xml.gz | 6.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4705 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4705 | HTTPS FTP |
-Related structure data
Related structure data | 6r1uMC 4704C 4710C 4711C 4712C 6r1tC 6r25C M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_4705.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | LSD/NPAC(214-225)/Nucleosome: Class 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
+Entire : LSD2/NPAC(214-225)/nucleosome
+Supramolecule #1: LSD2/NPAC(214-225)/nucleosome
+Supramolecule #2: Histone
+Supramolecule #3: DNA
+Supramolecule #4: Lysine-specific histone demethylase 1B
+Supramolecule #5: Putative oxidoreductase GLYR1
+Macromolecule #1: Histone H3.2
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A
+Macromolecule #4: Histone H2B 1.1
+Macromolecule #7: Lysine-specific histone demethylase 1B
+Macromolecule #8: Putative oxidoreductase GLYR1
+Macromolecule #9: Histone H3
+Macromolecule #5: DNA (147-MER)
+Macromolecule #6: DNA (147-MER)
+Macromolecule #10: FLAVIN-ADENINE DINUCLEOTIDE
+Macromolecule #11: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.87 mg/mL | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Buffer | pH: 7.5 Component:
| |||||||||
Vitrification | Cryogen name: ETHANE | |||||||||
Details | LSD2/NPAC(214-225)/nucleosome was monodisperse (gel filtration peak isolation and concentration in buffer described. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 2078 / Average exposure time: 8.0 sec. / Average electron dose: 1.25 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 0.0030499999999999998 µm / Nominal defocus min: 0.0007 µm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Initial model | PDB ID: Chain - Source name: PDB / Chain - Initial model type: experimental model |
---|---|
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
Output model | PDB-6r1u: |