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- PDB-9gvo: type-I interferons autoantibodies pmab15 and pmab14 in complex wi... -

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Basic information

Entry
Database: PDB / ID: 9gvo
Titletype-I interferons autoantibodies pmab15 and pmab14 in complex with Interferon alpha-2
Components
  • (scFv type-I interferons autoantibody ...) x 2
  • Interferon alpha-2
KeywordsIMMUNE SYSTEM / type-I interferon / Interferon alpha-2 / autoantibody / antigen antibody complex / COVID-19 pneumonia / Signaling Protein
Function / homology
Function and homology information


type I interferon receptor binding / B cell activation involved in immune response / negative regulation of interleukin-5 production / natural killer cell activation involved in immune response / negative regulation of interleukin-13 production / negative regulation of T cell differentiation / negative regulation of T-helper 2 cell cytokine production / T cell activation involved in immune response / host-mediated suppression of symbiont invasion / cell surface receptor signaling pathway via STAT ...type I interferon receptor binding / B cell activation involved in immune response / negative regulation of interleukin-5 production / natural killer cell activation involved in immune response / negative regulation of interleukin-13 production / negative regulation of T cell differentiation / negative regulation of T-helper 2 cell cytokine production / T cell activation involved in immune response / host-mediated suppression of symbiont invasion / cell surface receptor signaling pathway via STAT / TRAF6 mediated IRF7 activation / type I interferon-mediated signaling pathway / response to exogenous dsRNA / humoral immune response / Regulation of IFNA/IFNB signaling / cytokine activity / Evasion by RSV of host interferon responses / cellular response to virus / Interferon alpha/beta signaling / cell-cell signaling / : / Factors involved in megakaryocyte development and platelet production / defense response to virus / adaptive immune response / cell surface receptor signaling pathway / inflammatory response / negative regulation of gene expression / negative regulation of DNA-templated transcription / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / extracellular space / extracellular region
Similarity search - Function
Interferon alpha, beta and delta family signature. / Interferon alpha, beta and delta. / Interferon alpha/beta/delta / Interferon alpha/beta domain / Four-helical cytokine-like, core
Similarity search - Domain/homology
: / PHOSPHATE ION / Interferon alpha-2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.81 Å
AuthorsDuquerroy, S. / Rey, F. / Ahouzi, O. / Mahevas, M. / Chappert, P.
Funding support France, United States, 11items
OrganizationGrant numberCountry
French National Research AgencyANR-22-CE15-0047-01 France
French National Research AgencyANR-24-CHBS-0003 France
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01AI088364 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01AI163029 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R21AI160576 United States
French National Research AgencyANR-10-IAHU-01 France
French National Research AgencyANR-10-LABX-62-IBEID France
Fondation pour la Recherche Medicale (FRM)EQU201903007798 France
French National Research AgencyANR-20-CE93-003 France
French National Research AgencyANR-21-LIBA-0002 France
French National Research AgencyANR-21-RHUS-08 France
CitationJournal: To Be Published
Title: Temporal and structural insights into type-I interferons autoantibodies in severe COVID-19
Authors: Vanderkerken, M. / Fournier, M. / Dorgham, K. / Bastard, P. / Ahouzi, O. / Duquerroy, S. / Nguyen, N.K. / Broutin, M. / Charlet, M. / Vandenberghe, A. / Bizien, L. / Da Mata-Jardin, O. / ...Authors: Vanderkerken, M. / Fournier, M. / Dorgham, K. / Bastard, P. / Ahouzi, O. / Duquerroy, S. / Nguyen, N.K. / Broutin, M. / Charlet, M. / Vandenberghe, A. / Bizien, L. / Da Mata-Jardin, O. / Haouz, A. / Belmondo, T. / Hue, S. / Borghesi, A. / Rodriguez-Gallego, C. / Vinh, D. / Andreakos, V. / Haerynck, F. / Halwani, R. / Hammerstrom, T.Q.P. / Bjorkstrom, N. / Strunz, B. / Mogensen, T. / Trouillet, S. / Neven, B. / Rodriguez-Gallego, C. / Levy, R. / Le Voyer, T. / Delmonte, O. / O'Farrelly, C. / Riviere, J. / Amador Borrero, B. / Servettaz, A. / Crickx, E. / Michel, M. / Puel, A. / Abel, L. / Luyt, C.E. / Mathian, A. / Amoura, Z. / weill, J.C. / Casanova, J.L. / Rey, F.A. / Gorochov, G. / Chappert, P. / Mahevas, M.
History
DepositionSep 25, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 8, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: scFv type-I interferons autoantibody pmab14
B: Interferon alpha-2
H: scFv type-I interferons autoantibody pmab15
hetero molecules


Theoretical massNumber of molelcules
Total (without water)83,34512
Polymers82,5643
Non-polymers7829
Water6,918384
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: homology, antigen antibody complexes
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6090 Å2
ΔGint-24 kcal/mol
Surface area25500 Å2
Unit cell
Length a, b, c (Å)112.93, 112.93, 155.974
Angle α, β, γ (deg.)90, 90, 120
Int Tables number152
Space group name H-MP3121
Components on special symmetry positions
IDModelComponents
11A-502-

HOH

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Components

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Protein , 1 types, 1 molecules B

#2: Protein Interferon alpha-2 / IFN-alpha-2 / Interferon alpha-A / LeIF A


Mass: 21581.529 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IFNA2, IFNA2A, IFNA2B, IFNA2C / Cell line (production host): Schneider S2 Cell / Production host: Drosophila melanogaster (fruit fly) / References: UniProt: P01563

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Antibody , 2 types, 2 molecules AH

#1: Antibody scFv type-I interferons autoantibody pmab14


Mass: 30179.951 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Schneider S2 Cell / Production host: Drosophila melanogaster (fruit fly)
#3: Antibody scFv type-I interferons autoantibody pmab15


Mass: 30802.344 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Schneider S2 Cell / Production host: Drosophila melanogaster (fruit fly)

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Non-polymers , 4 types, 393 molecules

#4: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: PO4
#6: Chemical ChemComp-K / POTASSIUM ION


Mass: 39.098 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: K
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 384 / Source method: isolated from a natural source / Formula: H2O

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Details

Has ligand of interestN
Has protein modificationY

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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: 3.53 Å3/Da / Density % sol: 65 % / Description: cubic
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: 0.1 M Hepes pH 7.5 0.8 M Na2H2PO4 0.8 M KH2PO4

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.97857 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Sep 7, 2024
RadiationMonochromator: Si(111) crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97857 Å / Relative weight: 1
ReflectionResolution: 1.81→50 Å / Num. obs: 105167 / % possible obs: 100 % / Redundancy: 55.7 % / CC1/2: 1 / Rmerge(I) obs: 0.146 / Rpim(I) all: 0.019 / Rrim(I) all: 0.147 / Net I/σ(I): 17.1
Reflection shellResolution: 1.81→1.84 Å / Rmerge(I) obs: 5.184 / Mean I/σ(I) obs: 0.5 / Num. unique obs: 5103 / CC1/2: 0.353 / Rpim(I) all: 1.159 / Rrim(I) all: 5.313

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Processing

Software
NameVersionClassification
BUSTER2.10.4refinement
xia23.8.6data reduction
xia23.8.6data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.81→14.99 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.955 / SU R Cruickshank DPI: 0.086 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.088 / SU Rfree Blow DPI: 0.087 / SU Rfree Cruickshank DPI: 0.086
RfactorNum. reflection% reflectionSelection details
Rfree0.215 5205 -RANDOM
Rwork0.1925 ---
obs0.1936 104583 99.7 %-
Displacement parametersBiso mean: 50.17 Å2
Baniso -1Baniso -2Baniso -3
1--3.074 Å20 Å20 Å2
2---3.074 Å20 Å2
3---6.148 Å2
Refine analyzeLuzzati coordinate error obs: 0.24 Å
Refinement stepCycle: LAST / Resolution: 1.81→14.99 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4677 0 47 384 5108
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0094902HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.946652HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1671SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes839HARMONIC5
X-RAY DIFFRACTIONt_it4902HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion631SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies12HARMONIC1
X-RAY DIFFRACTIONt_ideal_dist_contact4324SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion3.98
X-RAY DIFFRACTIONt_other_torsion14.31
LS refinement shellResolution: 1.81→1.82 Å
RfactorNum. reflection% reflection
Rfree0.3788 108 -
Rwork0.3497 --
obs0.3512 2092 97.31 %
Refinement TLS params.

Refine-ID: X-RAY DIFFRACTION

IDL112)L122)L132)L222)L232)L332)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T112)T122)T132)T222)T232)T332)Origin x (Å)Origin y (Å)Origin z (Å)
11.045-0.0385-0.5757.6125-0.83592.9493-0.20430.02370.21290.02370.02440.47480.21290.47480.1799-0.01320.0889-0.05990.0719-0.0577-0.140485.0829-30.4152.6154
20.2614-0.42460.01130.6866-0.94131.9966-0.2172-0.06740.2695-0.06740.1759-0.18010.2695-0.18010.04130.03570.0454-0.00590.0453-0.0322-0.112977.0098-31.8485-0.7882
30.5193-0.74410.1041.01970.23341.1352-0.1067-0.01240.1081-0.01240.01660.09740.10810.09740.09010.01220.0470.0164-0.0393-0.0367-0.057278.7717-28.7117-7.7861
43.0443-1.5704-1.59342.08231.671800.2568-0.30390.0655-0.3039-0.3339-0.05150.0655-0.05150.07710.1360.14230.0075-0.0193-0.0182-0.133481.7074-34.8811-29.0507
51.091-1.0556-0.52531.30230.79090.43180.1201-0.23510.0012-0.2351-0.02090.11310.00120.1131-0.09910.05240.06020.0535-0.0531-0.0071-0.021282.8789-25.6754-21.8075
61.2843-1.5092-0.58021.45710.90920.39420.1022-0.1670.0913-0.167-0.07420.0660.09130.066-0.0280.09150.08780.029-0.0289-0.0189-0.052283.8791-33.938-22.2958
70.94351.34270.05971.99670.37430.56170.09580.01860.08670.0186-0.04640.0020.08670.002-0.04940.02950.02130.0128-0.10590.0131-0.014350.2488-15.4181-15.2336
83.4689-0.21332.38221.50361.69485.52970.1543-0.02610.189-0.02610.1103-0.20470.189-0.2047-0.26460.0436-0.01590.0207-0.0996-0.03690.019659.3063-7.646-9.0213
95.64790.17871.06533.80483.97570.83160.170.37370.47380.37370.158-0.07970.4738-0.0797-0.32790.09270.03360.0443-0.1392-0.13330.07352.5067-0.9541-5.7175
100.7043-0.93540.40941.12760.290.50640.0227-0.02870.0469-0.02870.1035-0.10560.0469-0.1056-0.12620.04980.00090.0123-0.1128-0.03030.010561.349-13.3728-12.7035
110.36140.34330.29522.7912-0.269700.007-0.14440.2914-0.14440.1829-0.37990.2914-0.3799-0.1898-0.0743-0.1207-0.03150.0686-0.0255-0.06631.9423-43.8295-27.4204
120.32590.80830.03750.82470.01430.92980.0111-0.05170.0182-0.0517-0.005-0.14090.0182-0.1409-0.00610.0017-0.0331-0.01540.01570.0015-0.046739.0927-34.7874-24.4954
133.4083-1.1345-0.90762.76350.99040.6585-0.193-0.4166-0.0803-0.41660.1877-0.103-0.0803-0.1030.0053-0.0103-0.044-0.04570.04620.0381-0.083139.7948-34.3082-32.0937
140.58330.4938-0.20581.5489-0.41880.71830.02480.11540.05650.1154-0.0617-0.20610.0565-0.20610.0369-0.0206-0.04610.0058-0.0101-0.0148-0.072941.6959-39.0277-20.0734
150.6196-0.9879-2.38511.5902-1.00342.25390.0610.24890.20320.2489-0.18290.23660.20320.23660.12190.1569-0.186-0.08660.02060.0362-0.229647.4522-43.81681.9215
163.3370.9009-1.59211.9179-1.49581.51150.05410.5237-0.30960.5237-0.23110.0452-0.30960.04520.1770.0896-0.1208-0.0316-0.04840.008-0.115450.128-33.7407-9.95
171.0411-0.8953-0.7222-0.022-2.50120.84770.01070.4293-0.49310.42930.2262-0.184-0.4931-0.184-0.23690.1133-0.07350.117-0.0294-0.0455-0.082438.0265-34.5538-4.712
18-0.7802-0.2349-3.68033.37170.55372.9529-0.00520.7277-0.00240.7277-0.2170.3075-0.00240.30750.22220.1109-0.1965-0.1015-0.01320.0162-0.25149.8687-35.3225-0.8125
190.5183-0.2042-1.37660.9272-0.19190-0.14320.3388-0.08110.3388-0.08710.0938-0.08110.09380.23030.1082-0.09450.04940.0006-0.0202-0.071539.9084-41.922-2.2537
200.93980.8073-1.41022.4786-2.33671.6477-0.1068-0.07-0.0102-0.07-0.1350.017-0.01020.0170.24180.0214-0.08570.00780.02020.0066-0.036145.604-43.9744-8.6454
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|3 - A|35 }A3 - 35
2X-RAY DIFFRACTION2{ A|36 - A|100 }A36 - 100
3X-RAY DIFFRACTION3{ A|101 - A|147 }A101 - 147
4X-RAY DIFFRACTION4{ A|148 - A|169 }A148 - 169
5X-RAY DIFFRACTION5{ A|170 - A|219 }A170 - 219
6X-RAY DIFFRACTION6{ A|220 - A|254 }A220 - 254
7X-RAY DIFFRACTION7{ B|8 - B|39 }B8 - 39
8X-RAY DIFFRACTION8{ B|40 - B|77 }B40 - 77
9X-RAY DIFFRACTION9{ B|78 - B|108 }B78 - 108
10X-RAY DIFFRACTION10{ B|109 - B|157 }B109 - 157
11X-RAY DIFFRACTION11{ H|3 - H|19 }H3 - 19
12X-RAY DIFFRACTION12{ H|20 - H|62 }H20 - 62
13X-RAY DIFFRACTION13{ H|63 - H|78 }H63 - 78
14X-RAY DIFFRACTION14{ H|79 - H|159 }H79 - 159
15X-RAY DIFFRACTION15{ H|160 - H|171 }H160 - 171
16X-RAY DIFFRACTION16{ H|172 - H|185 }H172 - 185
17X-RAY DIFFRACTION17{ H|186 - H|208 }H186 - 208
18X-RAY DIFFRACTION18{ H|209 - H|222 }H209 - 222
19X-RAY DIFFRACTION19{ H|223 - H|237 }H223 - 237
20X-RAY DIFFRACTION20{ H|238 - H|258 }H238 - 258

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