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- PDB-5w41: Zika MR766 NLS in complex with Importin alpha subunit-1 -

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Basic information

Entry
Database: PDB / ID: 5w41
TitleZika MR766 NLS in complex with Importin alpha subunit-1
Components
  • Importin subunit alpha-1
  • ZIKA MR766 NLS
Keywordsviral protein/protein binding / Zika / Nuclear Transport / Importin / Karyopherin / Virus / MR766 / viral protein-protein binding complex
Function / homology
Function and homology information


Sensing of DNA Double Strand Breaks / entry of viral genome into host nucleus through nuclear pore complex via importin / positive regulation of viral life cycle / NLS-dependent protein nuclear import complex / postsynapse to nucleus signaling pathway / nuclear import signal receptor activity / nuclear localization sequence binding / NLS-bearing protein import into nucleus / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin ...Sensing of DNA Double Strand Breaks / entry of viral genome into host nucleus through nuclear pore complex via importin / positive regulation of viral life cycle / NLS-dependent protein nuclear import complex / postsynapse to nucleus signaling pathway / nuclear import signal receptor activity / nuclear localization sequence binding / NLS-bearing protein import into nucleus / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / cytoplasmic stress granule / protein import into nucleus / host cell / double-stranded RNA binding / viral capsid / nucleoside-triphosphate phosphatase / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / symbiont-mediated suppression of host toll-like receptor signaling pathway / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell / DNA-binding transcription factor binding / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / postsynaptic density / host cell endoplasmic reticulum membrane / host cell perinuclear region of cytoplasm / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / serine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / glutamatergic synapse / viral envelope / lipid binding / host cell nucleus / virion attachment to host cell / GTP binding / structural molecule activity / virion membrane / ATP hydrolysis activity / proteolysis / extracellular region / nucleoplasm / ATP binding / membrane / nucleus / metal ion binding / cytosol
Similarity search - Function
Importin subunit alpha / Atypical Arm repeat / Importin-alpha, importin-beta-binding domain superfamily / Importin beta binding domain / Atypical Arm repeat / Importin-alpha, importin-beta-binding domain / IBB domain profile. / Armadillo/plakoglobin ARM repeat profile. / Armadillo/beta-catenin-like repeat / Armadillo/beta-catenin-like repeats ...Importin subunit alpha / Atypical Arm repeat / Importin-alpha, importin-beta-binding domain superfamily / Importin beta binding domain / Atypical Arm repeat / Importin-alpha, importin-beta-binding domain / IBB domain profile. / Armadillo/plakoglobin ARM repeat profile. / Armadillo/beta-catenin-like repeat / Armadillo/beta-catenin-like repeats / Armadillo / Leucine-rich Repeat Variant / Leucine-rich Repeat Variant / : / Flavivirus capsid protein C superfamily / RNA-directed RNA polymerase, thumb domain, Flavivirus / Flavivirus RNA-directed RNA polymerase, thumb domain / Flavivirus non-structural protein NS2B / Flavivirus envelope glycoprotein E, stem/anchor domain / : / Flavivirus NS3 helicase, C-terminal helical domain / Genome polyprotein, Flavivirus / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / Flavivirus non-structural protein NS4A / Flavivirus NS2B domain profile. / mRNA cap 0 and cap 1 methyltransferase (EC 2.1.1.56 and EC 2.1.1.57) domain profile. / Flavivirus non-structural protein NS2A / Flavivirus non-structural protein NS2A / Flavivirus NS3, petidase S7 / Peptidase S7, Flavivirus NS3 serine protease / Flavivirus NS3 protease (NS3pro) domain profile. / RNA-directed RNA polymerase, flavivirus / Flavivirus RNA-directed RNA polymerase, fingers and palm domains / Flavivirus non-structural Protein NS1 / Flavivirus non-structural protein NS1 / Envelope glycoprotein M, flavivirus / Flavivirus envelope glycoprotein M / Envelope glycoprotein M superfamily, flavivirus / Flavivirus polyprotein propeptide / Flavivirus polyprotein propeptide superfamily / Flavivirus polyprotein propeptide / Flaviviral glycoprotein E, central domain, subdomain 1 / Flaviviral glycoprotein E, central domain, subdomain 2 / Flavivirus envelope glycoprotein E, Stem/Anchor domain / Flavivirus glycoprotein E, immunoglobulin-like domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain superfamily / Flavivirus glycoprotein, immunoglobulin-like domain / Flavivirus glycoprotein central and dimerisation domain / Flavivirus glycoprotein, central and dimerisation domains / Ribosomal RNA methyltransferase, FtsJ domain / FtsJ-like methyltransferase / Flavivirus/Alphavirus glycoprotein, immunoglobulin-like domain superfamily / Flavivirus glycoprotein, central and dimerisation domain superfamily / Flaviviral glycoprotein E, dimerisation domain / DEAD box, Flavivirus / Flavivirus DEAD domain / Armadillo-like helical / Alpha Horseshoe / helicase superfamily c-terminal domain / Immunoglobulin E-set / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / Armadillo-type fold / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase / Mainly Alpha
Similarity search - Domain/homology
Importin subunit alpha-1 / Genome polyprotein
Similarity search - Component
Biological speciesMus musculus (house mouse)
Zika virus
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsJeffress, S. / Smith, K.M. / Forwood, J.K.
CitationJournal: ACS Infect Dis / Year: 2019
Title: Zika virus NS5 forms supramolecular nuclear bodies that sequester importin alpha and modulate the host immune and pro-inflammatory response in neuronal cells.
Authors: Ng, I.H.W. / Chan, K. / Tan, M.J.A. / Gwee, C.P. / Smith, K.M. / Jeffress, S.J. / Saw, W.G. / Swarbrick, C.M.D. / Watanabe, S. / Jans, D. / Gruber, G. / Forwood, J.K. / Vasudevan, S.G.
History
DepositionJun 8, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 13, 2018Provider: repository / Type: Initial release
Revision 1.1Mar 20, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Oct 4, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Importin subunit alpha-1
B: ZIKA MR766 NLS


Theoretical massNumber of molelcules
Total (without water)59,9412
Polymers59,9412
Non-polymers00
Water3,855214
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1230 Å2
ΔGint0 kcal/mol
Surface area18350 Å2
MethodPISA
Unit cell
Length a, b, c (Å)78.360, 89.230, 98.530
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

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Components

#1: Protein Importin subunit alpha-1 / Importin alpha P1 / Karyopherin subunit alpha-2 / Pendulin / Pore targeting complex 58 kDa subunit ...Importin alpha P1 / Karyopherin subunit alpha-2 / Pendulin / Pore targeting complex 58 kDa subunit / PTAC58 / RAG cohort protein 1 / SRP1-alpha


Mass: 55268.473 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Kpna2, Rch1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P52293
#2: Protein/peptide ZIKA MR766 NLS


Mass: 4672.485 Da / Num. of mol.: 1 / Fragment: unp residues 2887-2923
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Zika virus (strain Mr 766) / Strain: Mr 766 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q32ZE1
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 214 / 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: 2.87 Å3/Da / Density % sol: 57.19 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.5 / Details: 1M Sodium citrate, 0.01M DTT, pH6.5

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX1 / Wavelength: 0.9537 Å
DetectorType: ADSC QUANTUM 210r / Detector: CCD / Date: Jun 8, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9537 Å / Relative weight: 1
ReflectionResolution: 2.2→33.709 Å / Num. obs: 35736 / % possible obs: 100 % / Redundancy: 8 % / Net I/σ(I): 16.9

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Processing

Software
NameVersionClassification
PHENIX(1.10.1_2155: ???)refinement
iMOSFLMdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5FC8
Resolution: 2.2→33.709 Å / SU ML: 0.2 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 18.67
RfactorNum. reflection% reflection
Rfree0.2029 1801 5.04 %
Rwork0.1721 --
obs0.1737 35734 99.98 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 2.2→33.709 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3300 0 0 214 3514
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0093358
X-RAY DIFFRACTIONf_angle_d1.0294572
X-RAY DIFFRACTIONf_dihedral_angle_d14.352044
X-RAY DIFFRACTIONf_chiral_restr0.053551
X-RAY DIFFRACTIONf_plane_restr0.006585
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.2-2.25950.2391240.2192573X-RAY DIFFRACTION100
2.2595-2.32590.26491330.2142587X-RAY DIFFRACTION100
2.3259-2.4010.28421460.2142549X-RAY DIFFRACTION100
2.401-2.48680.23331290.20292585X-RAY DIFFRACTION100
2.4868-2.58630.25191250.20162594X-RAY DIFFRACTION100
2.5863-2.7040.2171420.19092602X-RAY DIFFRACTION100
2.704-2.84650.22641250.18142576X-RAY DIFFRACTION100
2.8465-3.02470.2091480.19062601X-RAY DIFFRACTION100
3.0247-3.25810.22481440.19012595X-RAY DIFFRACTION100
3.2581-3.58560.20771530.17042607X-RAY DIFFRACTION100
3.5856-4.10370.18111420.1442633X-RAY DIFFRACTION100
4.1037-5.16720.16081410.13562658X-RAY DIFFRACTION100
5.1672-33.71310.16951490.16082773X-RAY DIFFRACTION100

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