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- PDB-8cwu: Crystal structure of SARS-CoV-2 spike protein receptor-binding do... -

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Basic information

Entry
Database: PDB / ID: 8cwu
TitleCrystal structure of SARS-CoV-2 spike protein receptor-binding domain in complex with a cross-neutralizing nanobody 1-21
Components
  • Spike protein S1
  • VHH 1-21
KeywordsIMMUNE SYSTEM / cross-neutralizing antibody / nanobody / SARS-CoV-2 / Sarbecovirus / VHH
Function / homology
Function and homology information


Maturation of spike protein / viral translation / Translation of Structural Proteins / host cell surface / Virion Assembly and Release / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / host cell surface / Virion Assembly and Release / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / membrane fusion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / receptor ligand activity / endocytosis involved in viral entry into host cell / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane
Similarity search - Function
Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2 / Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
Biological speciesSevere acute respiratory syndrome coronavirus 2
Lama glama (llama)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.71 Å
AuthorsLiu, H. / Wilson, I.A.
Funding support United States, 1items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-004923 United States
CitationJournal: Cell Rep / Year: 2022
Title: Superimmunity by pan-sarbecovirus nanobodies.
Authors: Yufei Xiang / Wei Huang / Hejun Liu / Zhe Sang / Sham Nambulli / Jérôme Tubiana / Kevin L Williams / W Paul Duprex / Dina Schneidman-Duhovny / Ian A Wilson / Derek J Taylor / Yi Shi /
Abstract: Vaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observe superimmunity in a camelid extensively immunized with the ...Vaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observe superimmunity in a camelid extensively immunized with the SARS-CoV-2 receptor-binding domain (RBD). We rapidly isolate a large repertoire of specific ultra-high-affinity nanobodies that bind strongly to all known sarbecovirus clades using integrative proteomics. These pan-sarbecovirus nanobodies (psNbs) are highly effective against SARS-CoV and SARS-CoV-2 variants, including Omicron, with the best median neutralization potency at single-digit nanograms per milliliter. A highly potent, inhalable, and bispecific psNb (PiN-31) is also developed. Structural determinations of 13 psNbs with the SARS-CoV-2 spike or RBD reveal five epitope classes, providing insights into the mechanisms and evolution of their broad activities. The highly evolved psNbs target small, flat, and flexible epitopes that contain over 75% of conserved RBD surface residues. Their potencies are strongly and negatively correlated with the distance of the epitopes from the receptor binding sites.
History
DepositionMay 19, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 6, 2022Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2022Group: Database references / Category: citation / Item: _citation.journal_volume
Revision 1.2Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Spike protein S1
B: VHH 1-21
hetero molecules


Theoretical massNumber of molelcules
Total (without water)40,0463
Polymers39,4752
Non-polymers5711
Water4,810267
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2070 Å2
ΔGint5 kcal/mol
Surface area15490 Å2
MethodPISA
Unit cell
Length a, b, c (Å)119.151, 55.465, 59.561
Angle α, β, γ (deg.)90.000, 105.900, 90.000
Int Tables number5
Space group name H-MC121

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Components

#1: Protein Spike protein S1


Mass: 23104.867 Da / Num. of mol.: 1 / Fragment: Receptor binding domain, UNP residues 333-530
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P0DTC2
#2: Antibody VHH 1-21


Mass: 16370.241 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Lama glama (llama)
Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
#3: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 570.542 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4[LFucpa1-6]DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1221m-1a_1-5]/1-1-2/a4-b1_a6-c1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}[(6+1)][a-L-Fucp]{}}LINUCSPDB-CARE
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 267 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
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: 2.4 Å3/Da / Density % sol: 48.7 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 10.5
Details: 20% polyethylene glycol 8000, 0.1 M NaCl, 0.1 M CAPS pH 10.5

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1.0332 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Oct 31, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0332 Å / Relative weight: 1
ReflectionResolution: 1.71→50 Å / Num. obs: 39711 / % possible obs: 98.1 % / Redundancy: 3.9 % / Biso Wilson estimate: 14.71 Å2 / Rmerge(I) obs: 0.103 / Rpim(I) all: 0.058 / Rrim(I) all: 0.119 / Χ2: 0.894 / Net I/σ(I): 5.2 / Num. measured all: 154126
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.71-1.743.20.65918510.5130.3980.7760.79492.4
1.74-1.773.30.65519220.4490.3990.7730.77595.1
1.77-1.813.40.60219210.6190.3620.7070.78896.2
1.81-1.843.50.54819410.6150.3290.6440.81197.9
1.84-1.883.50.54419800.620.3270.6390.8697.6
1.88-1.933.70.49719820.6670.2940.5810.83498.2
1.93-1.973.70.42419840.780.2510.4960.90298.4
1.97-2.0340.37920090.8320.2150.4390.999.6
2.03-2.0940.32819980.8720.1870.3790.93799.6
2.09-2.1540.28620110.8960.1640.3320.95399.3
2.15-2.233.90.23619820.920.1360.2740.97699.1
2.23-2.323.90.19220260.9520.1080.2210.94498.7
2.32-2.434.10.16719830.9550.0940.1930.96898.6
2.43-2.554.20.13920060.9720.0770.160.94599.6
2.55-2.714.20.11820220.9770.0640.1351.0299.2
2.71-2.9240.09320010.9830.0520.1071.04598.6
2.92-3.224.20.07519950.9880.0410.0861.01898.6
3.22-3.684.40.05620450.9950.0290.0640.91599.3
3.68-4.644.10.04619990.9940.0250.0530.76497.8
4.64-504.30.04120530.9970.0210.0460.63697.5

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Processing

Software
NameVersionClassification
HKL-2000data scaling
PHENIX1.19.2_4158refinement
PDB_EXTRACT3.27data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 7JMW; 7KN5

7jmw

7kn5


Resolution: 1.71→47.54 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 20.83 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2032 1739 5.04 %
Rwork0.1851 32780 -
obs0.186 34519 84.93 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 103.83 Å2 / Biso mean: 24.2134 Å2 / Biso min: 6.12 Å2
Refinement stepCycle: final / Resolution: 1.71→47.54 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2495 0 38 267 2800
Biso mean--64.41 28.92 -
Num. residues----324
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 12

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.71-1.760.308620.25891210127238
1.76-1.820.255890.2411688177753
1.82-1.880.24991200.24142185230568
1.88-1.960.24531490.2242619276883
1.96-2.040.23221400.21242940308091
2.04-2.150.22991660.20173035320195
2.15-2.290.22621790.19693106328597
2.29-2.460.22061740.18783158333298
2.46-2.710.21681640.18873203336799
2.71-3.10.21041730.18653173334698
3.1-3.910.16461620.16623224338699
3.91-47.540.1591610.1523239340097
Refinement TLS params.Method: refined / Origin x: -31.5757 Å / Origin y: -2.1516 Å / Origin z: 19.9973 Å
111213212223313233
T0.096 Å2-0.0179 Å20.0062 Å2-0.0582 Å2-0.0183 Å2--0.0809 Å2
L1.9354 °2-0.5408 °20.3577 °2-0.5955 °2-0.0879 °2--0.5682 °2
S0.0313 Å °0.1231 Å °-0.0381 Å °-0.0794 Å °-0.0568 Å °0.0765 Å °0.0044 Å °0.0006 Å °0.0187 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allA334 - 528
2X-RAY DIFFRACTION1allA629 - 631
3X-RAY DIFFRACTION1allB-6 - 113
4X-RAY DIFFRACTION1allW1 - 267

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