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- PDB-7kn7: Crystal structure of SARS-CoV-2 receptor binding domain complexed... -
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Basic information
Entry | Database: PDB / ID: 7kn7 | |||||||||
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Title | Crystal structure of SARS-CoV-2 receptor binding domain complexed with nanobody VHH W and antibody Fab CC12.3 | |||||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Nanobody / Spike / Coronavirus / COVID-19 / IMMUNE SYSTEM / Nanobody-antigen complex / single-domain antibody / Antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus 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 / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / 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 | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Liu, H. / Yuan, M. / Zhu, X. / Wu, N.C. / Wilson, I.A. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape. Authors: Paul-Albert Koenig / Hrishikesh Das / Hejun Liu / Beate M Kümmerer / Florian N Gohr / Lea-Marie Jenster / Lisa D J Schiffelers / Yonas M Tesfamariam / Miki Uchima / Jennifer D Wuerth / Karl ...Authors: Paul-Albert Koenig / Hrishikesh Das / Hejun Liu / Beate M Kümmerer / Florian N Gohr / Lea-Marie Jenster / Lisa D J Schiffelers / Yonas M Tesfamariam / Miki Uchima / Jennifer D Wuerth / Karl Gatterdam / Natalia Ruetalo / Maria H Christensen / Caroline I Fandrey / Sabine Normann / Jan M P Tödtmann / Steffen Pritzl / Leo Hanke / Jannik Boos / Meng Yuan / Xueyong Zhu / Jonathan L Schmid-Burgk / Hiroki Kato / Michael Schindler / Ian A Wilson / Matthias Geyer / Kerstin U Ludwig / B Martin Hällberg / Nicholas C Wu / Florian I Schmidt / ![]() ![]() ![]() Abstract: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread, with devastating consequences. For passive immunization efforts, nanobodies have size and cost ...The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread, with devastating consequences. For passive immunization efforts, nanobodies have size and cost advantages over conventional antibodies. In this study, we generated four neutralizing nanobodies that target the receptor binding domain of the SARS-CoV-2 spike protein. We used x-ray crystallography and cryo-electron microscopy to define two distinct binding epitopes. On the basis of these structures, we engineered multivalent nanobodies with more than 100 times the neutralizing activity of monovalent nanobodies. Biparatopic nanobody fusions suppressed the emergence of escape mutants. Several nanobody constructs neutralized through receptor binding competition, whereas other monovalent and biparatopic nanobodies triggered aberrant activation of the spike fusion machinery. These premature conformational changes in the spike protein forestalled productive fusion and rendered the virions noninfectious. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 352.4 KB | Display | ![]() |
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PDB format | ![]() | 236.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7b14C ![]() 7b17C ![]() 7b18C ![]() 7kn5C ![]() 7kn6C ![]() 7ksgC ![]() 6waqS ![]() 6xc7S ![]() 7jmwS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 26095.348 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: S, 2 / Production host: ![]() |
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#2: Antibody | Mass: 15272.628 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#3: Antibody | Mass: 23377.150 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#4: Antibody | Mass: 23344.883 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#5: Sugar | ChemComp-NAG / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.15 Å3/Da / Density % sol: 61 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 1.0 M Li-chloride, 10% PEG-6000, 0.1 M Bicine pH 9.0 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jul 18, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.03317 Å / Relative weight: 1 |
Reflection | Resolution: 2.73→50 Å / Num. obs: 28107 / % possible obs: 98.1 % / Redundancy: 5.3 % / Biso Wilson estimate: 46.18 Å2 / CC1/2: 0.969 / Rmerge(I) obs: 0.181 / Rpim(I) all: 0.084 / Net I/σ(I): 9.3 |
Reflection shell | Resolution: 2.73→2.8 Å / Redundancy: 2.9 % / Rmerge(I) obs: 0.585 / Mean I/σ(I) obs: 1.1 / Num. unique obs: 1330 / CC1/2: 0.681 / Rpim(I) all: 0.37 / % possible all: 93 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 6XC7, 7JMW, 6WAQ Resolution: 2.73→49.18 Å / SU ML: 0.3802 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 27.1305 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 49.36 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.73→49.18 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 43.8301883298 Å / Origin y: 10.9088686176 Å / Origin z: 23.6498151984 Å
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Refinement TLS group | Selection details: all |