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- PDB-6pzh: Crystal structure of human NA-22 Fab -

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Basic information

Entry
Database: PDB / ID: 6pzh
TitleCrystal structure of human NA-22 Fab
Components
  • NA-22 Fab heavy chain
  • NA-22 Fab light chain
KeywordsIMMUNE SYSTEM / antibody / inhibition mechanism
Function / homologyImmunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Function and homology information
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsZhu, X. / Wilson, I.A.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)U19 AI117905 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)HHSN272201400024C United States
CitationJournal: Cell Host Microbe / Year: 2019
Title: Structural Basis of Protection against H7N9 Influenza Virus by Human Anti-N9 Neuraminidase Antibodies.
Authors: Xueyong Zhu / Hannah L Turner / Shanshan Lang / Ryan McBride / Sandhya Bangaru / Iuliia M Gilchuk / Wenli Yu / James C Paulson / James E Crowe / Andrew B Ward / Ian A Wilson /
Abstract: Influenza virus neuraminidase (NA) is a major target for small-molecule antiviral drugs. Antibodies targeting the NA surface antigen could also inhibit virus entry and egress to provide host ...Influenza virus neuraminidase (NA) is a major target for small-molecule antiviral drugs. Antibodies targeting the NA surface antigen could also inhibit virus entry and egress to provide host protection. However, our understanding of the nature and range of target epitopes is limited because of a lack of human antibody structures with influenza neuraminidase. Here, we describe crystal and cryogenic electron microscopy (cryo-EM) structures of NAs from human-infecting avian H7N9 viruses in complex with five human anti-N9 antibodies, systematically defining several antigenic sites and antibody epitope footprints. These antibodies either fully or partially block the NA active site or bind to epitopes distant from the active site while still showing neuraminidase inhibition. The inhibition of antibodies to NAs was further analyzed by glycan array and solution-based NA activity assays. Together, these structural studies provide insights into protection by anti-NA antibodies and templates for the development of NA-based influenza virus vaccines and therapeutics.
History
DepositionJul 31, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 4, 2019Provider: repository / Type: Initial release
Revision 1.1Dec 25, 2019Group: Database references / Category: citation / Item: _citation.journal_volume / _citation.page_first
Revision 1.2Oct 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
L: NA-22 Fab light chain
H: NA-22 Fab heavy chain
A: NA-22 Fab light chain
B: NA-22 Fab heavy chain


Theoretical massNumber of molelcules
Total (without water)96,4154
Polymers96,4154
Non-polymers00
Water6,143341
1
L: NA-22 Fab light chain
H: NA-22 Fab heavy chain


Theoretical massNumber of molelcules
Total (without water)48,2082
Polymers48,2082
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3600 Å2
ΔGint-24 kcal/mol
Surface area19300 Å2
MethodPISA
2
A: NA-22 Fab light chain
B: NA-22 Fab heavy chain


Theoretical massNumber of molelcules
Total (without water)48,2082
Polymers48,2082
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3640 Å2
ΔGint-24 kcal/mol
Surface area19150 Å2
MethodPISA
Unit cell
Length a, b, c (Å)72.269, 74.542, 178.266
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: Antibody NA-22 Fab light chain


Mass: 22890.076 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#2: Antibody NA-22 Fab heavy chain


Mass: 25317.467 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 341 / 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: 2.49 Å3/Da / Density % sol: 50.6 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 0.1 M Tris, pH 8.5, 40% ethanol, 0.02% magnium chloride

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL9-2 / Wavelength: 0.97946 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Nov 16, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 2.3→44.8 Å / Num. obs: 43271 / % possible obs: 99.3 % / Redundancy: 4.7 % / CC1/2: 0.996 / Rpim(I) all: 0.04 / Rsym value: 0.08 / Net I/σ(I): 23.4
Reflection shellResolution: 2.3→2.34 Å / Mean I/σ(I) obs: 2.2 / Num. unique obs: 2184 / CC1/2: 0.83 / Rpim(I) all: 0.25 / Rsym value: 0.48

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Processing

Software
NameVersionClassification
PHENIX(1.12_2829)refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5C2B, 4V1D

5c2b

4v1d


Resolution: 2.3→44.8 Å / SU ML: 0.27 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 24.01
RfactorNum. reflection% reflection
Rfree0.2364 2171 5.02 %
Rwork0.1931 --
obs0.1952 43207 98.34 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 2.3→44.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6531 0 0 341 6872
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0056695
X-RAY DIFFRACTIONf_angle_d0.7879132
X-RAY DIFFRACTIONf_dihedral_angle_d4.5813966
X-RAY DIFFRACTIONf_chiral_restr0.0571040
X-RAY DIFFRACTIONf_plane_restr0.0051163
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.2948-2.34470.30621100.26942168X-RAY DIFFRACTION84
2.3447-2.39920.28561340.23332576X-RAY DIFFRACTION100
2.3992-2.45920.30331370.232528X-RAY DIFFRACTION100
2.4592-2.52570.28921680.22712517X-RAY DIFFRACTION99
2.5257-2.60.29761370.2282538X-RAY DIFFRACTION98
2.6-2.68390.29861380.23242550X-RAY DIFFRACTION100
2.6839-2.77980.35761390.22782581X-RAY DIFFRACTION100
2.7798-2.89110.30551420.22262587X-RAY DIFFRACTION100
2.8911-3.02260.24451200.22542601X-RAY DIFFRACTION100
3.0226-3.1820.29841340.22582549X-RAY DIFFRACTION99
3.182-3.38120.23941360.21672619X-RAY DIFFRACTION100
3.3812-3.64220.25121390.19642580X-RAY DIFFRACTION100
3.6422-4.00850.20871210.19592617X-RAY DIFFRACTION99
4.0085-4.58810.1781320.15272625X-RAY DIFFRACTION99
4.5881-5.77860.16471330.14722667X-RAY DIFFRACTION99
5.7786-44.85080.20831510.16772733X-RAY DIFFRACTION98
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)
13.1527-1.54520.9061.0688-1.22510.65640.16580.5220.03120.1243-0.1805-0.15170.08060.20250.00080.2930.0394-0.01320.3601-0.02480.2874-1.156711.9303-9.3442
21.64370.8032-0.26721.097-0.5650.2169-0.1568-0.0221-0.0950.00730.02250.10340.1213-0.30610.00010.3902-0.04580.02720.3938-0.05340.3361-10.7969-14.4412-4.0859
31.1776-0.1681-0.73250.6977-0.51650.775-0.31950.7042-0.0695-0.13110.25110.12920.21050.0526-0.00010.4597-0.0720.00280.5193-0.08810.4149-10.0016-20.142-10.0652
41.18090.018-0.03872.0775-1.52150.83360.1690.1374-0.1317-0.118-0.1246-0.0010.0789-0.03480.00090.30120.0297-0.04460.3324-0.00870.2897-22.070615.642-14.6718
52.36680.9239-0.44961.12310.60570.9931-0.1572-0.18440.0642-0.03960.16920.1745-0.04890.349700.4058-0.00110.00040.5511-0.04960.4063-22.4958-17.97754.7065
62.0540.8609-1.79931.8822-1.16531.4566-0.1159-0.1208-0.2178-0.26680.07060.01560.1794-0.02890.00020.3606-0.02390.01470.25840.04970.33-5.9449-15.7736.272
71.5004-0.6497-0.5492.2770.2910.45910.11590.01810.0257-0.4568-0.15210.01720.0039-0.19580.00010.40520.0328-0.02750.36270.05240.3797-34.9523-6.874838.6198
82.24980.4854-1.13411.6317-0.78632.0469-0.05160.10350.094-0.14650.2120.2134-0.0252-0.08130.00230.3124-0.0313-0.00180.26860.0480.2593-2.88525.599727.83
90.62740.4821-0.57390.825-0.76581.25150.0850.11510.2113-0.16660.0186-0.00570.06880.05230.08270.35-0.02380.02550.30530.06620.3898-4.41582.031332.5148
102.865-2.25140.84261.6597-0.69370.9632-0.08-0.10420.22250.2957-0.0228-0.24520.08610.0632-0.00040.372-0.0206-0.0170.34180.02330.4082-35.26266.064948.5567
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'L' and (resid 3 through 106A)
2X-RAY DIFFRACTION2chain 'L' and (resid 107 through 172 )
3X-RAY DIFFRACTION3chain 'L' and (resid 173 through 214 )
4X-RAY DIFFRACTION4chain 'H' and (resid 1 through 119 )
5X-RAY DIFFRACTION5chain 'H' and (resid 120 through 230 )
6X-RAY DIFFRACTION6chain 'A' and (resid 1 through 106A)
7X-RAY DIFFRACTION7chain 'A' and (resid 107 through 214 )
8X-RAY DIFFRACTION8chain 'B' and (resid 1 through 87 )
9X-RAY DIFFRACTION9chain 'B' and (resid 88 through 119 )
10X-RAY DIFFRACTION10chain 'B' and (resid 120 through 230 )

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