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Open data
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Basic information
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Title | Cryo-EM structure of human METTL1-WDR4-tRNA(Val) complex | |||||||||
![]() | METTL1-WDR4-tRNA(Val) complex | |||||||||
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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 methylation / tRNA modification / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Li J / Wang L / Fontana P / Hunkeler M / Roy-Burman SS / Wu H / Fischer ES / Gregory RI | |||||||||
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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 117.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.2 KB 17.2 KB | Display Display | ![]() |
Images | ![]() | 76.1 KB | ||
Filedesc metadata | ![]() | 6.1 KB | ||
Others | ![]() ![]() | 116.2 MB 116.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ctiMC ![]() 7u20C ![]() 8cthC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | METTL1-WDR4-tRNA(Val) complex | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.825 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: METTL1-WDR4-tRNA(Val) complex
File | emd_26991_half_map_1.map | ||||||||||||
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Annotation | METTL1-WDR4-tRNA(Val) complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: METTL1-WDR4-tRNA(Val) complex
File | emd_26991_half_map_2.map | ||||||||||||
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Annotation | METTL1-WDR4-tRNA(Val) complex | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : METTL1-WDR4-tRNA_Val
Entire | Name: METTL1-WDR4-tRNA_Val |
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Components |
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-Supramolecule #1: METTL1-WDR4-tRNA_Val
Supramolecule | Name: METTL1-WDR4-tRNA_Val / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: tRNA (guanine-N(7)-)-methyltransferase, tRNA (guanine-N(7)-)-meth...
Supramolecule | Name: tRNA (guanine-N(7)-)-methyltransferase, tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4 type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: RNA
Supramolecule | Name: RNA / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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-Macromolecule #1: tRNA (guanine-N(7)-)-methyltransferase
Macromolecule | Name: tRNA (guanine-N(7)-)-methyltransferase / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: tRNA (guanine46-N7)-methyltransferase |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 31.516012 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MAAETRNVAG AEAPPPQKRY YRQRAHSNPM ADHTLRYPVK PEEMDWSELY PEFFAPLTQN QSHDDPKDKK EKRAQAQVEF ADIGCGYGG LLVELSPLFP DTLILGLEIR VKVSDYVQDR IRALRAAPAG GFQNIACLRS NAMKHLPNFF YKGQLTKMFF L FPDPHFKR ...String: MAAETRNVAG AEAPPPQKRY YRQRAHSNPM ADHTLRYPVK PEEMDWSELY PEFFAPLTQN QSHDDPKDKK EKRAQAQVEF ADIGCGYGG LLVELSPLFP DTLILGLEIR VKVSDYVQDR IRALRAAPAG GFQNIACLRS NAMKHLPNFF YKGQLTKMFF L FPDPHFKR TKHKWRIISP TLLAEYAYVL RVGGLVYTIT DVLELHDWMC THFEEHPLFE RVPLEDLSED PVVGHLGTST EE GKKVLRN GGKNFPAIFR RIQDPVLQAV TSQTSLPGH UniProtKB: tRNA (guanine-N(7)-)-methyltransferase |
-Macromolecule #2: tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4
Macromolecule | Name: tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 47.363516 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MGSSHHHHHH SQDPNSMAGS VGLALCGQTL VVRGGSRFLA TSIASSDDDS LFIYDCSAAE KKSQENKGED APLDQGSGAI LASTFSKSG SYFALTDDSK RLILFRTKPW QCLSVRTVAR RCTALTFIAS EEKVLVADKS GDVYSFSVLE PHGCGRLELG H LSMLLDVA ...String: MGSSHHHHHH SQDPNSMAGS VGLALCGQTL VVRGGSRFLA TSIASSDDDS LFIYDCSAAE KKSQENKGED APLDQGSGAI LASTFSKSG SYFALTDDSK RLILFRTKPW QCLSVRTVAR RCTALTFIAS EEKVLVADKS GDVYSFSVLE PHGCGRLELG H LSMLLDVA VSPDDRFILT ADRDEKIRVS WAAAPHSIES FCLGHTEFVS RISVVPTQPG LLLSSSGDGT LRLWEYRSGR QL HCCHLAS LQELVDPQAP QKFAASRIAF WCQENCVALL CDGTPVVYIF QLDARRQQLV YRQQLAFQHQ VWDVAFEETQ GLW VLQDCQ EAPLVLYRPV GDQWQSVPES TVLKKVSGVL RGNWAMLEGS AGADASFSSL YKATFDNVTS YLKKKEERLQ QQLE KKQRR RSPPPGPDGH AKKMRPGEAT LSC UniProtKB: tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4 |
-Macromolecule #3: tRNA-Val-TAC-2-1
Macromolecule | Name: tRNA-Val-TAC-2-1 / type: rna / ID: 3 / Number of copies: 1 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.451889 KDa |
Sequence | String: GGUUCCAUAG UGUAGCGGUU AUCACGUCUG CUUUACACGC AGAAGGUCCU GGGUUCGAGC CCCAGUGGAA CCA |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 51.8 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: INSILICO MODEL |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 11597 |