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- PDB-8h0n: Crystal structure of the human METTL1-WDR4 complex -

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Basic information

Entry
Database: PDB / ID: 8h0n
TitleCrystal structure of the human METTL1-WDR4 complex
Components
  • tRNA (guanine-N(7)-)-methyltransferase
  • tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4
KeywordsTRANSFERASE
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 / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat ...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 / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / 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)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.8 Å
AuthorsJin, X.H. / Guan, Z.Y. / Gong, Z. / Zhang, D.L.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)2017YFD0200400 China
CitationJournal: Cell Discov / Year: 2023
Title: Structural insight into how WDR4 promotes the tRNA N7-methylguanosine methyltransferase activity of METTL1.
Authors: Jin, X. / Guan, Z. / Hu, N. / He, C. / Yin, P. / Gong, Z. / Zhang, D.
History
DepositionSep 30, 2022Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jul 5, 2023Provider: repository / Type: Initial release
Revision 1.1Jul 12, 2023Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2Nov 8, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4
B: tRNA (guanine-N(7)-)-methyltransferase


Theoretical massNumber of molelcules
Total (without water)68,5792
Polymers68,5792
Non-polymers00
Water9,008500
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2020 Å2
ΔGint-5 kcal/mol
Surface area23850 Å2
MethodPISA
Unit cell
Length a, b, c (Å)84.465, 87.030, 95.915
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP22121
Space group name HallP22ab(z,x,y)
Symmetry operation#1: x,y,z
#2: x,-y,-z
#3: -x,y+1/2,-z+1/2
#4: -x,-y+1/2,z+1/2

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Components

#1: Protein tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4 / Protein Wuho homolog / hWH / WD repeat-containing protein 4


Mass: 40359.621 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: WDR4 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P57081
#2: Protein tRNA (guanine-N(7)-)-methyltransferase / Methyltransferase-like protein 1 / mRNA (guanine-N(7)-)-methyltransferase / miRNA (guanine-N(7)-)- ...Methyltransferase-like protein 1 / mRNA (guanine-N(7)-)-methyltransferase / miRNA (guanine-N(7)-)-methyltransferase / tRNA (guanine(46)-N(7))-methyltransferase / tRNA(m7G46)-methyltransferase


Mass: 28219.250 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: METTL1, C12orf1 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q9UBP6, tRNA (guanine46-N7)-methyltransferase, Transferases; Transferring one-carbon groups; Methyltransferases
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 500 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.57 Å3/Da / Density % sol: 52.15 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, hanging drop / Details: Bis-Tris, Lithium sulphate, PEG3350.

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL19U1 / Wavelength: 0.97918 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 13, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 1.8→45 Å / Num. obs: 66185 / % possible obs: 99.91 % / Redundancy: 2 % / Biso Wilson estimate: 22.67 Å2 / CC1/2: 0.997 / CC star: 0.999 / Rmerge(I) obs: 0.02884 / Rpim(I) all: 0.02884 / Rrim(I) all: 0.04079 / Net I/σ(I): 15.03
Reflection shellResolution: 1.8→1.864 Å / Redundancy: 2 % / Rmerge(I) obs: 0.1105 / Mean I/σ(I) obs: 5.57 / Num. unique obs: 13017 / CC1/2: 0.976 / CC star: 0.994 / Rpim(I) all: 0.1105 / Rrim(I) all: 0.1563 / % possible all: 99.98

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Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
HKL-2000data reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5IL2
Resolution: 1.8→38.68 Å / SU ML: 0.1875 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 22.8396
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2265 3203 4.84 %
Rwork0.1932 62982 -
obs0.1948 66185 99.86 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 34.13 Å2
Refinement stepCycle: LAST / Resolution: 1.8→38.68 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4251 0 0 500 4751
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00614356
X-RAY DIFFRACTIONf_angle_d0.84915909
X-RAY DIFFRACTIONf_chiral_restr0.0591654
X-RAY DIFFRACTIONf_plane_restr0.0069758
X-RAY DIFFRACTIONf_dihedral_angle_d13.89781567
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.8-1.830.23461360.212628X-RAY DIFFRACTION98.5
1.83-1.850.25211580.21392687X-RAY DIFFRACTION99.93
1.85-1.880.26131450.20632712X-RAY DIFFRACTION99.97
1.88-1.920.26881470.21872701X-RAY DIFFRACTION99.96
1.92-1.950.22371220.20912700X-RAY DIFFRACTION100
1.95-1.990.21831250.1982751X-RAY DIFFRACTION99.97
1.99-2.030.23751150.18882721X-RAY DIFFRACTION99.96
2.03-2.070.2261230.18572717X-RAY DIFFRACTION99.93
2.07-2.120.2431250.18562745X-RAY DIFFRACTION99.97
2.12-2.180.25621610.19472715X-RAY DIFFRACTION100
2.18-2.230.22181630.19282688X-RAY DIFFRACTION100
2.23-2.30.18271380.18772709X-RAY DIFFRACTION99.96
2.3-2.370.23581460.18762718X-RAY DIFFRACTION99.97
2.37-2.460.22271420.18972742X-RAY DIFFRACTION99.97
2.46-2.560.23951310.19612728X-RAY DIFFRACTION99.97
2.56-2.670.23631220.19392754X-RAY DIFFRACTION100
2.67-2.810.23151540.20182753X-RAY DIFFRACTION100
2.81-2.990.22091330.1952737X-RAY DIFFRACTION99.97
2.99-3.220.24131260.20132798X-RAY DIFFRACTION100
3.22-3.550.21311610.18652741X-RAY DIFFRACTION99.83
3.55-4.060.21371500.17562781X-RAY DIFFRACTION100
4.06-5.110.20521500.17232805X-RAY DIFFRACTION99.83
5.11-38.680.24691300.22362951X-RAY DIFFRACTION99.23
Refinement TLS params.Method: refined / Origin x: -23.4211915498 Å / Origin y: -2.19971051598 Å / Origin z: 19.0713524516 Å
111213212223313233
T0.156155318478 Å2-0.000825915899647 Å20.0103610824201 Å2-0.16449931191 Å20.00908888202177 Å2--0.139152473517 Å2
L0.180824029567 °2-0.238519047399 °20.0556618075933 °2-0.809055590067 °2-0.0763155039475 °2--0.0357184006626 °2
S0.0344661361215 Å °0.00474759805939 Å °0.00323688377145 Å °-0.0257852634795 Å °-0.0413052566648 Å °-0.115854240936 Å °-0.0215704741445 Å °-0.014730882525 Å °0.000240659900032 Å °
Refinement TLS groupSelection details: all

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