[English] 日本語
Yorodumi
- EMDB-26991: Cryo-EM structure of human METTL1-WDR4-tRNA(Val) complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-26991
TitleCryo-EM structure of human METTL1-WDR4-tRNA(Val) complex
Map dataMETTL1-WDR4-tRNA(Val) complex
Sample
  • Complex: METTL1-WDR4-tRNA_Val
    • Complex: tRNA (guanine-N(7)-)-methyltransferase, tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4
      • Protein or peptide: tRNA (guanine-N(7)-)-methyltransferase
      • Protein or peptide: tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4
    • Complex: RNA
      • RNA: tRNA-Val-TAC-2-1
Function / homology
Function and homology information


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 / enzyme activator activity / Transferases; Transferring one-carbon groups; Methyltransferases / chromosome / tRNA binding / DNA damage response / nucleolus / nucleoplasm / nucleus / cytosol
Similarity search - Function
tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit / tRNA (guanine-N-7) methyltransferase catalytic subunit Trm8, eukaryote / SAM-dependent methyltransferase TRMB-type domain profile. / tRNA (guanine-N-7) methyltransferase, Trmb type / Putative methyltransferase / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. ...tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit / tRNA (guanine-N-7) methyltransferase catalytic subunit Trm8, eukaryote / SAM-dependent methyltransferase TRMB-type domain profile. / tRNA (guanine-N-7) methyltransferase, Trmb type / Putative methyltransferase / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / S-adenosyl-L-methionine-dependent methyltransferase superfamily
Similarity search - Domain/homology
tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4 / tRNA (guanine-N(7)-)-methyltransferase
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsLi J / Wang L / Fontana P / Hunkeler M / Roy-Burman SS / Wu H / Fischer ES / Gregory RI
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R35CA232115 United States
CitationJournal: Nature / Year: 2023
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
DepositionMay 14, 2022-
Header (metadata) releaseDec 7, 2022-
Map releaseDec 7, 2022-
UpdateJan 25, 2023-
Current statusJan 25, 2023Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_26991.png

Downloads & links

-
Map

FileDownload / File: emd_26991.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationMETTL1-WDR4-tRNA(Val) complex
Voxel sizeX=Y=Z: 0.825 Å
Density
Contour LevelBy AUTHOR: 0.308
Minimum - Maximum-2.4018455 - 3.5969806
Average (Standard dev.)-0.0001636511 (±0.041395854)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 264.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: METTL1-WDR4-tRNA(Val) complex

Fileemd_26991_half_map_1.map
AnnotationMETTL1-WDR4-tRNA(Val) complex
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: METTL1-WDR4-tRNA(Val) complex

Fileemd_26991_half_map_2.map
AnnotationMETTL1-WDR4-tRNA(Val) complex
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : METTL1-WDR4-tRNA_Val

EntireName: METTL1-WDR4-tRNA_Val
Components
  • Complex: METTL1-WDR4-tRNA_Val
    • Complex: tRNA (guanine-N(7)-)-methyltransferase, tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4
      • Protein or peptide: tRNA (guanine-N(7)-)-methyltransferase
      • Protein or peptide: tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4
    • Complex: RNA
      • RNA: tRNA-Val-TAC-2-1

-
Supramolecule #1: METTL1-WDR4-tRNA_Val

SupramoleculeName: METTL1-WDR4-tRNA_Val / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all

-
Supramolecule #2: tRNA (guanine-N(7)-)-methyltransferase, tRNA (guanine-N(7)-)-meth...

SupramoleculeName: tRNA (guanine-N(7)-)-methyltransferase, tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4
type: complex / ID: 2 / Chimera: Yes / Parent: 1 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #3: RNA

SupramoleculeName: RNA / type: complex / ID: 3 / Chimera: Yes / Parent: 1 / Macromolecule list: #3

-
Macromolecule #1: tRNA (guanine-N(7)-)-methyltransferase

MacromoleculeName: tRNA (guanine-N(7)-)-methyltransferase / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: tRNA (guanine46-N7)-methyltransferase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 31.516012 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: 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

-
Macromolecule #2: tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4

MacromoleculeName: tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 47.363516 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: 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

-
Macromolecule #3: tRNA-Val-TAC-2-1

MacromoleculeName: tRNA-Val-TAC-2-1 / type: rna / ID: 3 / Number of copies: 1
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.451889 KDa
SequenceString:
GGUUCCAUAG UGUAGCGGUU AUCACGUCUG CUUUACACGC AGAAGGUCCU GGGUUCGAGC CCCAGUGGAA CCA

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 1.2 µm
Image recordingFilm 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

-
Image processing

Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 11597

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more