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- PDB-7sn1: Structure of human SARS-CoV-2 neutralizing antibody C1C-A3 Fab -

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Basic information

Entry
Database: PDB / ID: 7sn1
TitleStructure of human SARS-CoV-2 neutralizing antibody C1C-A3 Fab
Components
  • neutralizing antibody C1C-A3 Fab heavy chain
  • neutralizing antibody C1C-A3 Fab light chain
KeywordsIMMUNE SYSTEM / COVID-19 / SARS-CoV-2 / neutralizing antibody / neutralization escape
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.467 Å
AuthorsPan, J. / Abraham, J. / Clark, S.
Funding support United States, 1items
OrganizationGrant numberCountry
Other privateno grant number United States
CitationJournal: Science / Year: 2022
Title: Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain.
Authors: Katherine G Nabel / Sarah A Clark / Sundaresh Shankar / Junhua Pan / Lars E Clark / Pan Yang / Adrian Coscia / Lindsay G A McKay / Haley H Varnum / Vesna Brusic / Nicole V Tolan / Guohai ...Authors: Katherine G Nabel / Sarah A Clark / Sundaresh Shankar / Junhua Pan / Lars E Clark / Pan Yang / Adrian Coscia / Lindsay G A McKay / Haley H Varnum / Vesna Brusic / Nicole V Tolan / Guohai Zhou / Michaël Desjardins / Sarah E Turbett / Sanjat Kanjilal / Amy C Sherman / Anand Dighe / Regina C LaRocque / Edward T Ryan / Casey Tylek / Joel F Cohen-Solal / Anhdao T Darcy / Davide Tavella / Anca Clabbers / Yao Fan / Anthony Griffiths / Ivan R Correia / Jane Seagal / Lindsey R Baden / Richelle C Charles / Jonathan Abraham /
Abstract: Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we ...Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.
History
DepositionOct 27, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 8, 2021Provider: repository / Type: Initial release
Revision 1.1Dec 15, 2021Group: Database references / Category: citation / citation_author
Item: _citation.page_first / _citation.page_last ..._citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Feb 2, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.pdbx_database_id_DOI / _citation.year
Revision 1.3Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: neutralizing antibody C1C-A3 Fab heavy chain
L: neutralizing antibody C1C-A3 Fab light chain


Theoretical massNumber of molelcules
Total (without water)52,9192
Polymers52,9192
Non-polymers00
Water10,881604
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3210 Å2
ΔGint-22 kcal/mol
Surface area19500 Å2
MethodPISA
Unit cell
Length a, b, c (Å)62.736, 52.369, 71.394
Angle α, β, γ (deg.)90.00, 113.69, 90.00
Int Tables number4
Space group name H-MP1211

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Components

#1: Antibody neutralizing antibody C1C-A3 Fab heavy chain


Mass: 27022.607 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: mature antibody (after somatic hypermutation) from germline gene IGHV3-33
Source: (gene. exp.) Homo sapiens (human) / Gene: IGHV3-33 / Plasmid: pVRC8400
Cell line (production host): HEK-293 (Thermo Fisher Expi293F)
Production host: Homo sapiens (human)
#2: Antibody neutralizing antibody C1C-A3 Fab light chain


Mass: 25896.107 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: mature antibody (after somatic hypermutation) from germline gene IGKV3-11
Source: (gene. exp.) Homo sapiens (human) / Gene: IGKV3-11 / Plasmid: pVRC8400
Cell line (production host): HEK-293T (Thermo Fisher Expi293F)
Production host: Homo sapiens (human)
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 604 / 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: 2.03 Å3/Da / Density % sol: 39.39 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.9
Details: 18% PEG 8000, 0.02 M Magnesium chloride hexahydrate, and 0.1 M Tris pH 8.9
PH range: 7.5-8.9

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Data collection

DiffractionMean temperature: 80 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.97918 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Feb 22, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 1.467→200 Å / Num. obs: 137494 / % possible obs: 98.9 % / Redundancy: 2.19 % / Biso Wilson estimate: 27.486 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.059 / Rrim(I) all: 0.077 / Χ2: 0.89 / Net I/σ(I): 8.45
Reflection shellResolution: 1.467→1.56 Å / Redundancy: 2.17 % / Rmerge(I) obs: 0.934 / Mean I/σ(I) obs: 1.14 / Num. unique obs: 21177 / CC1/2: 0.336 / Rrim(I) all: 1.217 / Χ2: 0.73 / % possible all: 96.2

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Processing

Software
NameVersionClassification
BUSTER2.10.4refinement
O15.1.0model building
XDS20200131data reduction
XDS20200131data scaling
PHASER2.8.3phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: composite model generated from heavy and light chains from PDB codes 4DGV and 4PTU, respectively.

4dgv

4ptu


Resolution: 1.467→55.64 Å / Rfactor Rfree error: 26.11 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflection
Rfree0.206 3478 4.85 %
Rwork0.1779 --
obs0.1793 71663 98.5 %
Refinement stepCycle: LAST / Resolution: 1.467→55.64 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3301 0 0 604 3905
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0086760HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.0412165HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d2020SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes1090HARMONIC5
X-RAY DIFFRACTIONt_it3474HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion455SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies13HARMONIC1
X-RAY DIFFRACTIONt_ideal_dist_contact5743SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion4.59
X-RAY DIFFRACTIONt_other_torsion14.88
LS refinement shellResolution: 1.47→1.48 Å
RfactorNum. reflection% reflection
Rfree0.3425 78 -
Rwork0.2995 --
obs0.3018 1434 79.58 %
Refinement TLS params.

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)
10.254-0.1723-0.00990.87711.12861.35990.0015-0.0061-0.0071-0.00610.03910.0276-0.00710.0276-0.0406-0.00260.00110.0044-0.05890.0027-0.0159-64.1017-26.2995-31.1314
20.0718-0.09280.06430.1861-0.01290.04260.03730.0165-0.04380.0165-0.0261-0.0455-0.0438-0.0455-0.01120.0060.0105-0.0008-0.0205-0.0038-0.04-69.8671-36.1563-35.2624
30.31280.2125-0.16140.1923-0.30790.79220.0151-0.04270.0059-0.0427-0.0983-0.10130.0059-0.10130.0832-0.00250.00620.0026-0.0204-0.0023-0.0358-75.0955-31.3718-34.27
40.2977-0.09430.08640.1640.25270.01850.0086-0.0211-0.0073-0.02110.01870.0016-0.00730.0016-0.02740.00490.0060.005-0.0268-0.0001-0.0383-68.1111-35.9816-33.102
51.3711-0.15580.70030.1728-0.08090.58580.02840.0087-0.21550.0087-0.09780.078-0.21550.0780.0694-0.0048-0.0355-0.0209-0.00270.0045-0.0528-46.2775-23.1229-9.9597
60.7325-0.44590.00140.1359-0.4680.4226-0.0153-0.0542-0.0358-0.0542-0.09840.0448-0.03580.04480.1137-0.0355-0.01130.00430.00640.019-0.0316-43.2435-29.1038-13.1262
714.2745-0.54875.81710.0374-1.01212.35660.07-0.1702-0.527-0.1702-0.37680.3136-0.5270.31360.30680.0164-0.05620.00290.07680.0147-0.0083-39.2194-21.1492-15.9472
83.72160.81840.54040.11450.6063-0.24230.15590.1472-0.01580.14720.0119-0.0954-0.0158-0.0954-0.1678-0.0119-0.0061-0.0486-0.02810.0006-0.0126-59.8141-55.2291-18.5121
90.52810.20030.18480.0973-0.02410.11280.00210.01810.01350.0181-0.01130.00020.01350.00020.0092-0.0226-0.0021-0.0039-0.0202-0.0016-0.0188-62.9045-52.9767-27.9883
100.7236-0.74510.37080.0510.49481.5994-0.032-0.0262-0.1256-0.02620.1560.1327-0.12560.1327-0.124-0.0124-0.02270.0093-0.01290.0123-0.0866-46.5761-36.6412-5.3955
110.1973-0.8131-0.27871.01971.38381.64940.02970.02380.04250.0238-0.017-0.06580.0425-0.0658-0.0127-0.0084-0.02530.01220.01150.0038-0.0559-49.8586-40.9754-0.1818
12-0.4174-0.3664-0.25140.24340.86595.2838-0.01950.00090.09650.00090.0873-0.24210.0965-0.2421-0.0678-0.0183-0.002-0.00310.047-0.0009-0.0917-54.5272-32.30283.5309
131.7859-0.73810.18522.84891.09853.6483-0.07740.1161-0.42230.11610.21210.1285-0.42230.1285-0.1347-0.00940.00170.01530.0650.0149-0.0423-46.7523-32.80352.6756
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ H|1 - H|17 }H1 - 17
2X-RAY DIFFRACTION2{ H|18 - H|59 }H18 - 59
3X-RAY DIFFRACTION3{ H|60 - H|75 }H60 - 75
4X-RAY DIFFRACTION4{ H|76 - H|111 }H76 - 111
5X-RAY DIFFRACTION5{ H|112 - H|145 }H112 - 145
6X-RAY DIFFRACTION6{ H|146 - H|191 }H146 - 191
7X-RAY DIFFRACTION7{ H|192 - H|213 }H192 - 213
8X-RAY DIFFRACTION8{ L|1 - L|18 }L1 - 18
9X-RAY DIFFRACTION9{ L|19 - L|98 }L19 - 98
10X-RAY DIFFRACTION10{ L|99 - L|137 }L99 - 137
11X-RAY DIFFRACTION11{ L|138 - L|150 }L138 - 150
12X-RAY DIFFRACTION12{ L|151 - L|163 }L151 - 163
13X-RAY DIFFRACTION13{ L|164 - L|212 }L164 - 212

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