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Open data
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Basic information
Entry | Database: PDB / ID: 8d5b | ||||||||||||
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Title | Crystal structure of human METTL1 in complex with SAH | ||||||||||||
![]() | tRNA (guanine-N(7)-)-methyltransferase | ||||||||||||
![]() | TRANSFERASE / Cancer protein | ||||||||||||
Function / homology | ![]() internal mRNA (guanine-N7-)-methyltransferase activity / tRNA (m7G46) methyltransferase complex / tRNA stabilization / tRNA (guanine-N7)-methylation / RNA (guanine-N7)-methylation / tRNA (guanine46-N7)-methyltransferase / tRNA (guanine(46)-N7)-methyltransferase activity / tRNA methyltransferase complex / tRNA modification in the nucleus and cytosol / tRNA modification ...internal mRNA (guanine-N7-)-methyltransferase activity / tRNA (m7G46) methyltransferase complex / tRNA stabilization / tRNA (guanine-N7)-methylation / RNA (guanine-N7)-methylation / tRNA (guanine46-N7)-methyltransferase / tRNA (guanine(46)-N7)-methyltransferase activity / tRNA methyltransferase complex / tRNA modification in the nucleus and cytosol / tRNA modification / tRNA methylation / cellular response to stress / Transferases; Transferring one-carbon groups; Methyltransferases / tRNA binding / nucleolus / nucleoplasm / nucleus / cytosol Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ![]() ![]() ![]() | ||||||||||||
![]() | Raj, R. / Babu, K. / Nam, Y. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures and mechanisms of tRNA methylation by METTL1-WDR4. Authors: Victor M Ruiz-Arroyo / Rishi Raj / Kesavan Babu / Otgonbileg Onolbaatar / Paul H Roberts / Yunsun Nam / ![]() Abstract: Specific, regulated modification of RNAs is important for proper gene expression. tRNAs are rich with various chemical modifications that affect their stability and function. 7-Methylguanosine (mG) ...Specific, regulated modification of RNAs is important for proper gene expression. tRNAs are rich with various chemical modifications that affect their stability and function. 7-Methylguanosine (mG) at tRNA position 46 is a conserved modification that modulates steady-state tRNA levels to affect cell growth. The METTL1-WDR4 complex generates mG46 in humans, and dysregulation of METTL1-WDR4 has been linked to brain malformation and multiple cancers. Here we show how METTL1 and WDR4 cooperate to recognize RNA substrates and catalyse methylation. A crystal structure of METTL1-WDR4 and cryo-electron microscopy structures of METTL1-WDR4-tRNA show that the composite protein surface recognizes the tRNA elbow through shape complementarity. The cryo-electron microscopy structures of METTL1-WDR4-tRNA with S-adenosylmethionine or S-adenosylhomocysteine along with METTL1 crystal structures provide additional insights into the catalytic mechanism by revealing the active site in multiple states. The METTL1 N terminus couples cofactor binding with conformational changes in the tRNA, the catalytic loop and the WDR4 C terminus, acting as the switch to activate mG methylation. Thus, our structural models explain how post-translational modifications of the METTL1 N terminus can regulate methylation. Together, our work elucidates the core and regulatory mechanisms underlying mG modification by METTL1, providing the framework to understand its contribution to biology and disease. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 74.3 KB | Display | ![]() |
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PDB format | ![]() | 41.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 769.4 KB | Display | ![]() |
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Full document | ![]() | 770.7 KB | Display | |
Data in XML | ![]() | 11.7 KB | Display | |
Data in CIF | ![]() | 16 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8d58C ![]() 8d59C ![]() 8d9kC ![]() 8d9lC ![]() 8eg0C ![]() 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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1 |
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Unit cell |
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Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 30412.713 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q9UBP6, tRNA (guanine46-N7)-methyltransferase, Transferases; Transferring one-carbon groups; Methyltransferases |
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-Non-polymers , 6 types, 151 molecules 










#2: Chemical | ChemComp-SAH / | ||||||||
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#3: Chemical | #4: Chemical | #5: Chemical | ChemComp-CL / | #6: Chemical | ChemComp-CAC / | #7: Water | ChemComp-HOH / | |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.46 Å3/Da / Density % sol: 49.97 % |
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Crystal grow | Temperature: 295.15 K / Method: vapor diffusion, hanging drop Details: 50 mM Sodium cacodylate pH 5.7, 1.5 M Lithium sulfate, 10 mM Magnesium sulfate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 2, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9789 Å / Relative weight: 1 |
Reflection | Resolution: 1.93→37.25 Å / Num. obs: 20856 / % possible obs: 100 % / Redundancy: 18.1 % / Biso Wilson estimate: 32.6 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.242 / Rpim(I) all: 0.057 / Net I/σ(I): 16.24 |
Reflection shell | Resolution: 1.93→1.96 Å / Redundancy: 10.5 % / Rmerge(I) obs: 3.22 / Mean I/σ(I) obs: 1.3 / Num. unique obs: 1034 / CC1/2: 0.45 / Rpim(I) all: 1.03 / % possible all: 99.9 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 3CKK Resolution: 1.93→37.25 Å / SU ML: 0.2564 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 24.2094 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: 36.9 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.93→37.25 Å
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Refine LS restraints |
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LS refinement shell |
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