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Yorodumi- PDB-7x2k: Crystal structure of nanobody Nb70 with antibody 1F11 fab and SAR... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7x2k | ||||||
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Title | Crystal structure of nanobody Nb70 with antibody 1F11 fab and SARS-CoV-2 RBD | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / nanobody / spike / receptor binding domain / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | Function and homology information 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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / 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 | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) Vicugna pacos (alpaca) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å | ||||||
Authors | Wang, X.Q. / Zhang, L.Q. / Ren, Y.F. / Li, M.X. | ||||||
Funding support | 1items
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Citation | Journal: Nat Commun / Year: 2022 Title: Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses. Authors: Mingxi Li / Yifei Ren / Zhen Qin Aw / Bo Chen / Ziqing Yang / Yuqing Lei / Lin Cheng / Qingtai Liang / Junxian Hong / Yiling Yang / Jing Chen / Yi Hao Wong / Jing Wei / Sisi Shan / Senyan ...Authors: Mingxi Li / Yifei Ren / Zhen Qin Aw / Bo Chen / Ziqing Yang / Yuqing Lei / Lin Cheng / Qingtai Liang / Junxian Hong / Yiling Yang / Jing Chen / Yi Hao Wong / Jing Wei / Sisi Shan / Senyan Zhang / Jiwan Ge / Ruoke Wang / Jay Zengjun Dong / Yuxing Chen / Xuanling Shi / Qi Zhang / Zheng Zhang / Justin Jang Hann Chu / Xinquan Wang / Linqi Zhang / Abstract: As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we ...As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7x2k.cif.gz | 299.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7x2k.ent.gz | 243.1 KB | Display | PDB format |
PDBx/mmJSON format | 7x2k.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7x2k_validation.pdf.gz | 468.7 KB | Display | wwPDB validaton report |
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Full document | 7x2k_full_validation.pdf.gz | 476.3 KB | Display | |
Data in XML | 7x2k_validation.xml.gz | 29.2 KB | Display | |
Data in CIF | 7x2k_validation.cif.gz | 41.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x2/7x2k ftp://data.pdbj.org/pub/pdb/validation_reports/x2/7x2k | HTTPS FTP |
-Related structure data
Related structure data | 7x2jC 7x2lC 7x2mC 6m0jS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Antibody , 3 types, 3 molecules HLB
#2: Antibody | Mass: 22851.592 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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#3: Antibody | Mass: 23274.766 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#4: Antibody | Mass: 14071.498 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Vicugna pacos (alpaca) / Production host: Bacillus (Bacillus rRNA group 1) |
-Protein / Sugars / Non-polymers , 3 types, 218 molecules E
#1: Protein | Mass: 21776.381 Da / Num. of mol.: 1 / Fragment: RBD Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P0DTC2 |
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#5: Sugar | ChemComp-NAG / |
#6: Water | ChemComp-HOH / |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.87 Å3/Da / Density % sol: 57.19 % |
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Crystal grow | Temperature: 291.15 K / Method: vapor diffusion, sitting drop Details: 0.15M DL-Malic acid pH 7.0, 20% w/v Polyethylene glycol 3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL18U1 / Wavelength: 0.987 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 22, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.987 Å / Relative weight: 1 |
Reflection | Resolution: 2.4→45.62 Å / Num. obs: 37441 / % possible obs: 99.54 % / Redundancy: 12.2 % / CC1/2: 0.995 / Net I/σ(I): 17.18 |
Reflection shell | Resolution: 2.4→2.486 Å / Num. unique obs: 3677 / CC1/2: 0.618 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6m0j Resolution: 2.4→45.62 Å / SU ML: 0.33 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 25.66 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.4→45.62 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: 10.0344 Å / Origin y: 25.1361 Å / Origin z: -0.878 Å
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Refinement TLS group | Selection details: all |