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Yorodumi- PDB-8p7c: CryoEM structure of METTL6 tRNA SerRS complex in a 2:2:2 stoichiometry -
+Open data
-Basic information
Entry | Database: PDB / ID: 8p7c | ||||||
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Title | CryoEM structure of METTL6 tRNA SerRS complex in a 2:2:2 stoichiometry | ||||||
Components |
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Keywords | RNA BINDING PROTEIN / METTL6 / tRNA / SerRS / Serine tRNA / 3-Methylcytosine | ||||||
Function / homology | Function and homology information selenocysteine-tRNA ligase activity / tRNA (cytidine-3-)-methyltransferase activity / negative regulation of vascular endothelial growth factor production / selenocysteine incorporation / seryl-tRNA aminoacylation / serine-tRNA ligase / serine-tRNA ligase activity / Cytosolic tRNA aminoacylation / tRNA modification / tRNA methylation ...selenocysteine-tRNA ligase activity / tRNA (cytidine-3-)-methyltransferase activity / negative regulation of vascular endothelial growth factor production / selenocysteine incorporation / seryl-tRNA aminoacylation / serine-tRNA ligase / serine-tRNA ligase activity / Cytosolic tRNA aminoacylation / tRNA modification / tRNA methylation / Selenocysteine synthesis / negative regulation of angiogenesis / Transferases; Transferring one-carbon groups; Methyltransferases / cytoplasmic translation / tRNA binding / molecular adaptor activity / translation / RNA polymerase II cis-regulatory region sequence-specific DNA binding / enzyme binding / negative regulation of transcription by RNA polymerase II / protein homodimerization activity / extracellular exosome / ATP binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Trichoplusia ni (cabbage looper) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||
Authors | Throll, P. / Dolce, L.G. / Kowalinski, E. | ||||||
Funding support | 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: Structural basis of tRNA recognition by the mC RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase. Authors: Philipp Throll / Luciano G Dolce / Palma Rico-Lastres / Katharina Arnold / Laura Tengo / Shibom Basu / Stefanie Kaiser / Robert Schneider / Eva Kowalinski / Abstract: Methylation of cytosine 32 in the anticodon loop of tRNAs to 3-methylcytosine (mC) is crucial for cellular translation fidelity. Misregulation of the RNA methyltransferases setting this modification ...Methylation of cytosine 32 in the anticodon loop of tRNAs to 3-methylcytosine (mC) is crucial for cellular translation fidelity. Misregulation of the RNA methyltransferases setting this modification can cause aggressive cancers and metabolic disturbances. Here, we report the cryo-electron microscopy structure of the human mC tRNA methyltransferase METTL6 in complex with seryl-tRNA synthetase (SerRS) and their common substrate tRNA. Through the complex structure, we identify the tRNA-binding domain of METTL6. We show that SerRS acts as the tRNA substrate selection factor for METTL6. We demonstrate that SerRS augments the methylation activity of METTL6 and that direct contacts between METTL6 and SerRS are necessary for efficient tRNA methylation. Finally, on the basis of the structure of METTL6 in complex with SerRS and tRNA, we postulate a universal tRNA-binding mode for mC RNA methyltransferases, including METTL2 and METTL8, suggesting that these mammalian paralogs use similar ways to engage their respective tRNA substrates and cofactors. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8p7c.cif.gz | 338.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8p7c.ent.gz | 264.4 KB | Display | PDB format |
PDBx/mmJSON format | 8p7c.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8p7c_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 8p7c_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8p7c_validation.xml.gz | 76 KB | Display | |
Data in CIF | 8p7c_validation.cif.gz | 108.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/p7/8p7c ftp://data.pdbj.org/pub/pdb/validation_reports/p7/8p7c | HTTPS FTP |
-Related structure data
Related structure data | 17529MC 8owxC 8owyC 8p7bC 8p7dC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 4 molecules BDAC
#1: Protein | Mass: 58863.211 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SARS1, SARS, SERS / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P49591, serine-tRNA ligase #2: Protein | Mass: 33296.055 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: METTL6 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q8TCB7, Transferases; Transferring one-carbon groups; Methyltransferases |
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-RNA chain , 1 types, 2 molecules RT
#3: RNA chain | Mass: 27620.635 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Trichoplusia ni (cabbage looper) |
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-Non-polymers , 3 types, 10 molecules
#4: Chemical | #5: Chemical | ChemComp-MG / #6: Water | ChemComp-HOH / | |
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-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 | Name: METTL6 tRNA SerRS complex in a 2:2:2 stoichiometry / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
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 / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 63.27 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 105928 / Symmetry type: POINT | ||||||||||||||||||||||||
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