+Open data
-Basic information
Entry | Database: PDB / ID: 7epu | ||||||
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Title | Crystal structure of HsALC1 | ||||||
Components |
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Keywords | MOTOR PROTEIN / macrodomain / autoinhibition / DNA damage / PARP1 | ||||||
Function / homology | Function and homology information poly-ADP-D-ribose modification-dependent protein binding / ATP-dependent chromatin remodeler activity / site of DNA damage / nucleosome binding / DNA helicase activity / histone reader 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 / site of double-strand break ...poly-ADP-D-ribose modification-dependent protein binding / ATP-dependent chromatin remodeler activity / site of DNA damage / nucleosome binding / DNA helicase activity / histone reader 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 / site of double-strand break / chromatin remodeling / nucleotide binding / DNA repair / DNA damage response / ATP hydrolysis activity / nucleoplasm / ATP binding / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.5 Å | ||||||
Authors | Wang, L. / Chen, K.J. | ||||||
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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7epu.cif.gz | 214.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7epu.ent.gz | 165.4 KB | Display | PDB format |
PDBx/mmJSON format | 7epu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ep/7epu ftp://data.pdbj.org/pub/pdb/validation_reports/ep/7epu | HTTPS FTP |
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-Related structure data
Related structure data | 7ennC 2fg1S 3mwyS 5jxrS 5yanS S: Starting model for refinement 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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Unit cell |
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-Components
#1: Antibody | Mass: 27769.326 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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#2: Protein | Mass: 99392.242 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 |
#3: Chemical | ChemComp-ADP / |
#4: Chemical | ChemComp-MG / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.62 Å3/Da / Density % sol: 66.03 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / Details: MPD, sodium chloride, magnesium chloride, acetate |
-Data collection
Diffraction | Mean temperature: 277 K / Serial crystal experiment: N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 0.97 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Oct 24, 2019 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 3.5→50 Å / Num. obs: 23523 / % possible obs: 99.4 % / Redundancy: 10.8 % / Biso Wilson estimate: 127.58 Å2 / Rmerge(I) obs: 0.13 / Rpim(I) all: 0.042 / Rrim(I) all: 0.137 / Χ2: 0.811 / Net I/σ(I): 5.5 / Num. measured all: 255064 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3MWY, 5JXR, 2FG1, 5YAN Resolution: 3.5→45.402 Å / SU ML: 0.56 / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 35.23 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 262.94 Å2 / Biso mean: 141.9093 Å2 / Biso min: 41.31 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 3.5→45.402 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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