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- PDB-9gvl: type-I interferons autoantibody pmab15 in complex with Interferon... -

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Basic information

Entry
Database: PDB / ID: 9gvl
Titletype-I interferons autoantibody pmab15 in complex with Interferon alpha-2
Components
  • Interferon alpha-2
  • scFv type-I interferons autoantibody pmab15
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
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.006 Å
AuthorsDuquerroy, S. / Rey, F. / Mahevas, M. / Chappert, P. / Ahouzi, O.
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: Interferon alpha-2
B: Interferon alpha-2
H: scFv type-I interferons autoantibody pmab15
I: scFv type-I interferons autoantibody pmab15
hetero molecules


Theoretical massNumber of molelcules
Total (without water)105,1488
Polymers104,7684
Non-polymers3804
Water5,170287
1
A: Interferon alpha-2
H: scFv type-I interferons autoantibody pmab15
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,4803
Polymers52,3842
Non-polymers961
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Interferon alpha-2
I: scFv type-I interferons autoantibody pmab15
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,6685
Polymers52,3842
Non-polymers2843
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)66.159, 83.719, 70.264
Angle α, β, γ (deg.)90, 113.8, 90
Int Tables number4
Space group name H-MP1211

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Components

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


Mass: 21581.529 Da / Num. of mol.: 2
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
#2: Antibody scFv type-I interferons autoantibody pmab15


Mass: 30802.344 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IFNA2 / Cell line (production host): Schneider S2 Cell / Production host: Drosophila melanogaster (fruit fly)
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 287 / Source method: isolated from a natural source / Formula: H2O
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: 1.78 Å3/Da / Density % sol: 31 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 4.6
Details: 0.2 M (NH4)2SO4 0.1 M NaAcetate pH 4.6 30 %w/w PEG 2000 MME

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 2 / Wavelength: 0.953721 Å
DetectorType: DECTRIS EIGER2 X 9M / Detector: PIXEL / Date: Jun 28, 2024
Details: Cryogenically cooled channel cut crystal monochromator, a convex prefocussing mirror and a Kirkpatrick-Baez pair of focussing mirrors
RadiationMonochromator: SI(111) CRYSTAL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.953721 Å / Relative weight: 1
ReflectionResolution: 2→65 Å / Num. obs: 46986 / % possible obs: 100 % / Redundancy: 5 % / CC1/2: 0.991 / Rmerge(I) obs: 0.202 / Rpim(I) all: 0.098 / Rrim(I) all: 0.225 / Net I/σ(I): 3.6
Reflection shellResolution: 2.006→2.041 Å / Redundancy: 5.1 % / Rmerge(I) obs: 2.611 / Mean I/σ(I) obs: 0.6 / Num. unique obs: 2310 / CC1/2: 0.373 / Rpim(I) all: 1.667 / Rrim(I) all: 2.902 / % possible all: 99.7

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Processing

Software
NameVersionClassification
BUSTER2.10.4refinement
XDSJun 30, 2023 (BUILT 20230630)data reduction
autoPROC1.0.5 (20240123)data reduction
Aimless0.7.15data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.006→14.97 Å / Cor.coef. Fo:Fc: 0.951 / Cor.coef. Fo:Fc free: 0.922 / SU R Cruickshank DPI: 0.219 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.217 / SU Rfree Blow DPI: 0.19 / SU Rfree Cruickshank DPI: 0.193
RfactorNum. reflection% reflectionSelection details
Rfree0.2696 2428 -RANDOM
Rwork0.2143 ---
obs0.217 46627 99.5 %-
Displacement parametersBiso mean: 46.83 Å2
Baniso -1Baniso -2Baniso -3
1-6.0191 Å20 Å2-0.9795 Å2
2---0.9393 Å20 Å2
3----5.0798 Å2
Refine analyzeLuzzati coordinate error obs: 0.31 Å
Refinement stepCycle: LAST / Resolution: 2.006→14.97 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5645 0 21 287 5953
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0085793HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.917842HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1952SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes985HARMONIC5
X-RAY DIFFRACTIONt_it5793HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion735SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact5061SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion3.51
X-RAY DIFFRACTIONt_other_torsion16.25
LS refinement shellResolution: 2.01→2.02 Å
RfactorNum. reflection% reflection
Rfree0.3705 49 -
Rwork0.388 --
obs0.3871 933 90.59 %
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)
16.6241-1.1125-1.40890.6972-1.26581.31470.22420.3718-0.18220.3718-0.16180.3815-0.18220.3815-0.0624-0.1458-0.05210.0612-0.05440.02190.154143.6845-3.593224.154
26.0942-0.8741-1.08600.34160.1954-0.0140.1179-0.04090.1179-0.16810.3942-0.04090.39420.1821-0.2201-0.00090.04970.09240.06020.100853.753-8.880824.8295
36.69063.68970.67371.1349-1.15330.12510.31140.3601-0.46440.3601-0.23590.1834-0.46440.1834-0.0754-0.0701-0.02990.10930.0399-0.03580.14244.3608-5.226724.5273
48.689-0.27361.07970.2897-0.11371.5001-0.12380.0101-0.37840.01010.18140.2631-0.37840.2631-0.0576-0.1845-0.05550.01470.0384-0.0625-0.004166.4317-22.271358.5325
57.19042.8764-3.406700.69055.5290.0487-0.07420.0611-0.0742-0.49130.28970.06110.28970.4426-0.2729-0.07370.09750.304-0.1986-0.042777.9111-21.185652.499
67.02082.57461.44463.11551.37470.2314-0.1784-0.2432-0.4829-0.24320.1814-0.2139-0.4829-0.2139-0.0031-0.1450.036-0.00760.11180.00010.036765.5323-21.211465.1486
74.1274-0.03251.13740.1014-0.02940.5657-0.15540.0642-0.00320.06420.00720.0704-0.00320.07040.1482-0.0954-0.03240.0358-0.0697-0.01950.181415.71-3.555119.7519
81.8034-0.0362-0.06640.50770.5470.5521-0.09760.0680.06250.068-0.0654-0.03750.0625-0.03750.163-0.03710.0281-0.0287-0.0887-0.04520.182624.04464.500237.5399
93.72070.45190.66640.98260.96480.64320.1263-0.3151-0.2127-0.3151-0.0196-0.1576-0.2127-0.1576-0.1067-0.05090.022-0.02040.12790.0767-0.078834.2907-24.36154.2761
103.3908-1.32790.67641.2673-0.1243-0.063-0.2337-0.2034-0.0148-0.20340.1031-0.1639-0.0148-0.16390.13070.01510.0568-0.06570.0884-0.1411-0.026142.2807-5.113458.2881
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|8 - A|51 }A8 - 51
2X-RAY DIFFRACTION2{ A|52 - A|136 }A52 - 136
3X-RAY DIFFRACTION3{ A|137 - A|156 }A137 - 156
4X-RAY DIFFRACTION4{ B|8 - B|77 }B8 - 77
5X-RAY DIFFRACTION5{ B|78 - B|99 }B78 - 99
6X-RAY DIFFRACTION6{ B|112 - B|156 }B112 - 156
7X-RAY DIFFRACTION7{ H|3 - H|126 }H3 - 126
8X-RAY DIFFRACTION8{ H|147 - H|255 }H147 - 255
9X-RAY DIFFRACTION9{ I|3 - I|126 }I3 - 126
10X-RAY DIFFRACTION10{ I|147 - I|255 }I147 - 255

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