+Open data
-Basic information
Entry | Database: PDB / ID: 7enn | ||||||
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Title | The structure of ALC1 bound to the nucleosome | ||||||
Components |
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Keywords | DNA BINDING PROTEIN / Complex | ||||||
Function / homology | Function and homology information poly-ADP-D-ribose modification-dependent protein binding / ATP-dependent chromatin remodeler activity / histone reader activity / site of DNA damage / nucleosome binding / DNA helicase activity / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / Dual Incision in GG-NER / Formation of Incision Complex in GG-NER / structural constituent of chromatin ...poly-ADP-D-ribose modification-dependent protein binding / ATP-dependent chromatin remodeler activity / histone reader activity / site of DNA damage / nucleosome binding / DNA helicase activity / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / Dual Incision in GG-NER / Formation of Incision Complex in GG-NER / structural constituent of chromatin / nucleosome / nucleosome assembly / site of double-strand break / chromatin remodeling / protein heterodimerization activity / DNA repair / nucleotide binding / DNA damage response / ATP hydrolysis activity / DNA binding / nucleoplasm / ATP binding / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Xenopus laevis (African clawed frog) synthetic construct (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
Authors | Chen, Z.C. / Chen, K.J. / Wang, L. | ||||||
Citation | Journal: Nat Commun / Year: 2021 Title: Structural basis of ALC1/CHD1L autoinhibition and the mechanism of activation by the nucleosome. Authors: Li Wang / Kangjing Chen / Zhucheng Chen / Abstract: Chromatin remodeler ALC1 (amplification in liver cancer 1) is crucial for repairing damaged DNA. It is autoinhibited and activated by nucleosomal epitopes. However, the mechanisms by which ALC1 is ...Chromatin remodeler ALC1 (amplification in liver cancer 1) is crucial for repairing damaged DNA. It is autoinhibited and activated by nucleosomal epitopes. However, the mechanisms by which ALC1 is regulated remain unclear. Here we report the crystal structure of human ALC1 and the cryoEM structure bound to the nucleosome. The structure shows the macro domain of ALC1 binds to lobe 2 of the ATPase motor, sequestering two elements for nucleosome recognition, explaining the autoinhibition mechanism of the enzyme. The H4 tail competes with the macro domain for lobe 2-binding, explaining the requirement for this nucleosomal epitope for ALC1 activation. A dual-arginine-anchor motif of ALC1 recognizes the acidic pocket of the nucleosome, which is critical for chromatin remodeling in vitro. Together, our findings illustrate the structures of ALC1 and shed light on its regulation mechanisms, paving the way for the discovery of drugs targeting ALC1 for the treatment of cancer. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7enn.cif.gz | 378.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7enn.ent.gz | 296.9 KB | Display | PDB format |
PDBx/mmJSON format | 7enn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7enn_validation.pdf.gz | 897.4 KB | Display | wwPDB validaton report |
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Full document | 7enn_full_validation.pdf.gz | 916.7 KB | Display | |
Data in XML | 7enn_validation.xml.gz | 44.9 KB | Display | |
Data in CIF | 7enn_validation.cif.gz | 70.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/en/7enn ftp://data.pdbj.org/pub/pdb/validation_reports/en/7enn | HTTPS FTP |
-Related structure data
Related structure data | 31217MC 7epuC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 5 types, 9 molecules KAELFCGDH
#1: Protein | Mass: 101117.094 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CHD1L, ALC1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q86WJ1, DNA helicase | ||||||
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#2: Protein | Mass: 15289.904 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P84233 #3: Protein | Mass: 11263.231 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P62799 #4: Protein | Mass: 13978.241 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P06897 #5: Protein | Mass: 13524.752 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P02281 |
-DNA chain , 2 types, 2 molecules IJ
#6: DNA chain | Mass: 51311.652 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#7: DNA chain | Mass: 51800.965 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-Non-polymers , 2 types, 2 molecules
#8: Chemical | ChemComp-ADP / |
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#9: Chemical | ChemComp-BEF / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 586673 / Symmetry type: POINT |