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- PDB-6u1t: Crystal structure of anti-Nipah virus (NiV) F 5B3 antibody Fab fr... -

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Basic information

Entry
Database: PDB / ID: 6u1t
TitleCrystal structure of anti-Nipah virus (NiV) F 5B3 antibody Fab fragment
Components
  • antigen-binding (Fab) fragment, heavy chain
  • antigen-binding (Fab) fragment, light chain
KeywordsIMMUNE SYSTEM / Nipah virus / Hendra virus / Henipavirus / Fusion glycoprotein / antibody neutralization / Fab / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID
Function / homologyImmunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Function and homology information
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.483 Å
AuthorsDang, H.V. / Chan, Y.P. / Park, Y.J. / Snijder, J. / Da Silva, S.C. / Vu, B. / Yan, L. / Feng, Y.R. / Rockx, B. / Geisbert, T. ...Dang, H.V. / Chan, Y.P. / Park, Y.J. / Snijder, J. / Da Silva, S.C. / Vu, B. / Yan, L. / Feng, Y.R. / Rockx, B. / Geisbert, T. / Mire, C. / Mire, C.E. / BBroder, C.C. / Veesler, D. / Seattle Structural Genomics Center for Infectious Disease (SSGCID)
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM120553 United States
CitationJournal: Nat Struct Mol Biol / Year: 2019
Title: An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections.
Authors: Ha V Dang / Yee-Peng Chan / Young-Jun Park / Joost Snijder / Sofia Cheliout Da Silva / Bang Vu / Lianying Yan / Yan-Ru Feng / Barry Rockx / Thomas W Geisbert / Chad E Mire / Christopher C ...Authors: Ha V Dang / Yee-Peng Chan / Young-Jun Park / Joost Snijder / Sofia Cheliout Da Silva / Bang Vu / Lianying Yan / Yan-Ru Feng / Barry Rockx / Thomas W Geisbert / Chad E Mire / Christopher C Broder / David Veesler /
Abstract: Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50-100%. No vaccines or licensed ...Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50-100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.
History
DepositionAug 16, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 9, 2019Provider: repository / Type: Initial release
Revision 1.1Nov 13, 2019Group: 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.identifier_ORCID / _citation_author.name
Revision 1.2Nov 27, 2019Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.3Jan 1, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Oct 11, 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

Downloads & links

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Assembly

Deposited unit
H: antigen-binding (Fab) fragment, heavy chain
L: antigen-binding (Fab) fragment, light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)47,1613
Polymers47,1252
Non-polymers351
Water10,034557
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3680 Å2
ΔGint-41 kcal/mol
Surface area19710 Å2
MethodPISA
Unit cell
Length a, b, c (Å)78.120, 95.010, 137.200
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number20
Space group name H-MC2221

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Components

#1: Antibody antigen-binding (Fab) fragment, heavy chain


Mass: 23678.463 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Cell: hybridoma / Cell (production host): hybridoma / Production host: Mus musculus (house mouse)
#2: Antibody antigen-binding (Fab) fragment, light chain


Mass: 23446.893 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Cell: hybridoma / Cell (production host): hybridoma / Production host: Mus musculus (house mouse)
#3: Chemical ChemComp-CL / CHLORIDE ION / Chloride


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 557 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN

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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: 2.7 Å3/Da / Density % sol: 54.46 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.5
Details: 0.2 M Magnesium chloride, 0.1 M Tris HCl, pH 8.5 and 20% PEG 8000

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Data collection

DiffractionMean temperature: 80 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 0.9774 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jun 27, 2018
RadiationMonochromator: Single crystal, cylindrically bent, Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9774 Å / Relative weight: 1
ReflectionResolution: 1.48→68.6 Å / Num. obs: 84268 / % possible obs: 99.7 % / Redundancy: 5.6 % / Rpim(I) all: 0.036 / Rrim(I) all: 0.088 / Rsym value: 0.08 / Net I/av σ(I): 6.3 / Net I/σ(I): 10.2
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsRpim(I) allRrim(I) allRsym value% possible all
1.483-1.563.60.9040.9119650.5231.0520.90497.8
1.56-1.665.30.6261.2115820.2990.6950.626100
1.66-1.775.80.4011.9108730.1810.4410.401100
1.77-1.9160.2353.2101690.1040.2580.235100
1.91-2.16.10.1455.193540.0640.1580.145100
2.1-2.346.10.1136.185140.050.1230.113100
2.34-2.716.10.0897.575190.0390.0970.089100
2.71-3.326.20.0610.564020.0260.0660.06100
3.32-4.6960.04513.350220.020.050.045100
4.69-68.660.0413.728680.0180.0440.04100

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Phasing

PhasingMethod: molecular replacement
Phasing MRModel details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation6.38 Å68.6 Å
Translation6.38 Å68.6 Å

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Processing

Software
NameVersionClassificationNB
REFMAC5.8.0222refinement
MOSFLMdata reduction
SCALA3.3.22data scaling
PHASER2.8.2phasing
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6NB8

6nb8


Resolution: 1.483→68.6 Å / Cor.coef. Fo:Fc: 0.979 / Cor.coef. Fo:Fc free: 0.97 / SU B: 3.593 / SU ML: 0.055 / SU R Cruickshank DPI: 0.0647 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.065 / ESU R Free: 0.06
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.1733 4238 5 %RANDOM
Rwork0.1372 ---
obs0.139 79965 99.61 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 86.68 Å2 / Biso mean: 21.717 Å2 / Biso min: 10.72 Å2
Baniso -1Baniso -2Baniso -3
1--3.94 Å2-0 Å20 Å2
2--3.27 Å2-0 Å2
3---0.68 Å2
Refinement stepCycle: final / Resolution: 1.483→68.6 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3296 0 1 557 3854
Biso mean--37.86 41.05 -
Num. residues----435
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0143736
X-RAY DIFFRACTIONr_bond_other_d0.0010.0173253
X-RAY DIFFRACTIONr_angle_refined_deg1.221.6555190
X-RAY DIFFRACTIONr_angle_other_deg0.911.6367740
X-RAY DIFFRACTIONr_dihedral_angle_1_deg14.485.276561
X-RAY DIFFRACTIONr_dihedral_angle_2_deg30.14423.113151
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.44915606
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.1251513
X-RAY DIFFRACTIONr_chiral_restr0.0610.2530
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.024739
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02733
X-RAY DIFFRACTIONr_rigid_bond_restr3.22536989
X-RAY DIFFRACTIONr_sphericity_free41.884571
X-RAY DIFFRACTIONr_sphericity_bonded23.3257335
LS refinement shellResolution: 1.483→1.522 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.34 304 -
Rwork0.308 5659 -
all-5963 -
obs--96.16 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.03730.00480.02130.01010.01180.0211-0.0001-0.00060.00160.00020.00110.0006-0.00080.0008-0.0010.042500.00050.00020.00010.015768.27662.080456.2965
20.0102-0.0110.00670.0182-0.01740.0215-0.0002-0.00120.0012-0.0007-0.00080.00060.00040.00290.0010.0429-0.0005-0.00030.0010.00070.016557.673663.687521.2859
30.0176-0.005-0.00150.0148-0.01770.0354-0.0004-0.0007-0.0003-0.00030.0014-0.0011-0.00020.0002-0.0010.0416-0.00010.00040.000400.01659.787882.593153.621
40.020.0340.01980.06050.0340.0358-0.0001-0.0012-0.0003-0.0037-0.0006-0.00080.000400.00070.04340.00010.00010.0008-0.00010.01643.181369.1423.4584
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1H1 - 118
2X-RAY DIFFRACTION2H119 - 221
3X-RAY DIFFRACTION3L1 - 110
4X-RAY DIFFRACTION4L111 - 214

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