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Open data
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Basic information
Entry | Database: PDB / ID: 7u20 | ||||||||||||
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Title | Crystal structure of human METTL1 and WDR4 complex | ||||||||||||
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![]() | TRANSFERASE / METTL1 WDR4 tRNA methyltransferase | ||||||||||||
Function / homology | ![]() internal mRNA (guanine-N7-)-methyltransferase activity / tRNA stabilization / tRNA (m7G46) methyltransferase complex / tRNA (guanine-N7)-methylation / RNA (guanine-N7)-methylation / tRNA (guanine46-N7)-methyltransferase / tRNA (guanine(46)-N7)-methyltransferase activity / tRNA methyltransferase activator activity / tRNA methyltransferase complex / tRNA modification in the nucleus and cytosol ...internal mRNA (guanine-N7-)-methyltransferase activity / tRNA stabilization / tRNA (m7G46) methyltransferase complex / tRNA (guanine-N7)-methylation / RNA (guanine-N7)-methylation / tRNA (guanine46-N7)-methyltransferase / tRNA (guanine(46)-N7)-methyltransferase activity / tRNA methyltransferase activator activity / tRNA methyltransferase complex / tRNA modification in the nucleus and cytosol / tRNA modification / tRNA methylation / enzyme activator activity / Transferases; Transferring one-carbon groups; Methyltransferases / chromosome / tRNA binding / DNA damage response / nucleolus / nucleoplasm / nucleus / cytosol Similarity search - Function | ||||||||||||
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Method | ![]() ![]() ![]() | ||||||||||||
![]() | Li, J. / Nowak, R.P. / Fischer, E.S. / Gregory, R. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of regulated mG tRNA modification by METTL1-WDR4. Authors: Jiazhi Li / Longfei Wang / Quentin Hahn / Radosław P Nowak / Thibault Viennet / Esteban A Orellana / Shourya S Roy Burman / Hong Yue / Moritz Hunkeler / Pietro Fontana / Hao Wu / Haribabu ...Authors: Jiazhi Li / Longfei Wang / Quentin Hahn / Radosław P Nowak / Thibault Viennet / Esteban A Orellana / Shourya S Roy Burman / Hong Yue / Moritz Hunkeler / Pietro Fontana / Hao Wu / Haribabu Arthanari / Eric S Fischer / Richard I Gregory / ![]() ![]() Abstract: Chemical modifications of RNA have key roles in many biological processes. N-methylguanosine (mG) is required for integrity and stability of a large subset of tRNAs. The methyltransferase 1-WD repeat- ...Chemical modifications of RNA have key roles in many biological processes. N-methylguanosine (mG) is required for integrity and stability of a large subset of tRNAs. The methyltransferase 1-WD repeat-containing protein 4 (METTL1-WDR4) complex is the methyltransferase that modifies G46 in the variable loop of certain tRNAs, and its dysregulation drives tumorigenesis in numerous cancer types. Mutations in WDR4 cause human developmental phenotypes including microcephaly. How METTL1-WDR4 modifies tRNA substrates and is regulated remains elusive. Here we show, through structural, biochemical and cellular studies of human METTL1-WDR4, that WDR4 serves as a scaffold for METTL1 and the tRNA T-arm. Upon tRNA binding, the αC region of METTL1 transforms into a helix, which together with the α6 helix secures both ends of the tRNA variable loop. Unexpectedly, we find that the predicted disordered N-terminal region of METTL1 is part of the catalytic pocket and essential for methyltransferase activity. Furthermore, we reveal that S27 phosphorylation in the METTL1 N-terminal region inhibits methyltransferase activity by locally disrupting the catalytic centre. Our results provide a molecular understanding of tRNA substrate recognition and phosphorylation-mediated regulation of METTL1-WDR4, and reveal the presumed disordered N-terminal region of METTL1 as a nexus of methyltransferase activity. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 144.5 KB | Display | ![]() |
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PDB format | ![]() | 94.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 20.1 KB | Display | |
Data in CIF | ![]() | 26.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8cthC ![]() 8ctiC ![]() 2vduS ![]() 3ckkS S: Starting model for refinement C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 31516.012 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Residues not visible in the structure have not been modeled. Recombinant protein did not have any affinity tags. Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q9UBP6, tRNA (guanine46-N7)-methyltransferase, Transferases; Transferring one-carbon groups; Methyltransferases | ||||
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#2: Protein | Mass: 47363.516 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: MGSSHHHHHHSQDPNS is part of the expression tag and a linker. Residues not visible in the structure have not been modeled. Source: (gene. exp.) ![]() ![]() ![]() | ||||
#3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.39 Å3/Da / Density % sol: 63.79 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: 2M (NH4)2SO4, 0.2M K Na Tartrate, 0.1 M Na3 citrate pH 6.5 Temp details: Room temperature |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Dec 2, 2020 / Details: monochromatros | ||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97918 Å / Relative weight: 1 | ||||||||||||||||||||||||
Reflection | Resolution: 3.09→47.87 Å / Num. obs: 19262 / % possible obs: 99 % / Redundancy: 4.6 % / Biso Wilson estimate: 85.6 Å2 / Rmerge(I) obs: 0.308 / Rpim(I) all: 0.214 / Rrim(I) all: 0.377 / Net I/σ(I): 5.1 | ||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 3CKK for METTL1, chain D of 2VDU for WDR4 Resolution: 3.1→47.87 Å / SU ML: 0.4274 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 28.9413 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 75.05 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.1→47.87 Å
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Refine LS restraints |
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LS refinement shell |
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