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Open data
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Basic information
Entry | Database: PDB / ID: 8d47 | ||||||
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Title | fp.006 Fab in complex with SARS-CoV-2 Fusion Peptide | ||||||
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![]() | ANTIVIRAL PROTEIN / antibody / fusion peptide / TMPRSS2 binding site / 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 | ![]() ![]() ![]() | ||||||
![]() | Abernathy, M.E. / Barnes, C.O. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein. Authors: Filippo Bianchini / Virginia Crivelli / Morgan E Abernathy / Concetta Guerra / Martin Palus / Jonathan Muri / Harold Marcotte / Antonio Piralla / Mattia Pedotti / Raoul De Gasparo / Luca ...Authors: Filippo Bianchini / Virginia Crivelli / Morgan E Abernathy / Concetta Guerra / Martin Palus / Jonathan Muri / Harold Marcotte / Antonio Piralla / Mattia Pedotti / Raoul De Gasparo / Luca Simonelli / Milos Matkovic / Chiara Toscano / Maira Biggiogero / Veronica Calvaruso / Pavel Svoboda / Tomás Cervantes Rincón / Tommaso Fava / Lucie Podešvová / Akanksha A Shanbhag / Andrea Celoria / Jacopo Sgrignani / Michal Stefanik / Vaclav Hönig / Veronika Pranclova / Tereza Michalcikova / Jan Prochazka / Giuditta Guerrini / Dora Mehn / Annalisa Ciabattini / Hassan Abolhassani / David Jarrossay / Mariagrazia Uguccioni / Donata Medaglini / Qiang Pan-Hammarström / Luigi Calzolai / Daniel Fernandez / Fausto Baldanti / Alessandra Franzetti-Pellanda / Christian Garzoni / Radislav Sedlacek / Daniel Ruzek / Luca Varani / Andrea Cavalli / Christopher O Barnes / Davide F Robbiani / ![]() ![]() ![]() ![]() ![]() ![]() Abstract: Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies ...Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2' site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants. #1: Journal: bioRxiv / Year: 2022 Title: Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2. Authors: Filippo Bianchini / Virginia Crivelli / Morgan E Abernathy / Concetta Guerra / Martin Palus / Jonathan Muri / Harold Marcotte / Antonio Piralla / Mattia Pedotti / Raoul De Gasparo / Luca ...Authors: Filippo Bianchini / Virginia Crivelli / Morgan E Abernathy / Concetta Guerra / Martin Palus / Jonathan Muri / Harold Marcotte / Antonio Piralla / Mattia Pedotti / Raoul De Gasparo / Luca Simonelli / Milos Matkovic / Chiara Toscano / Maira Biggiogero / Veronica Calvaruso / Pavel Svoboda / Tomás Cervantes Rincón / Tommaso Fava / Lucie Podešvová / Akanksha A Shanbhag / Andrea Celoria / Jacopo Sgrignani / Michal Stefanik / Vaclav Hönig / Veronika Pranclova / Tereza Michalcikova / Jan Prochazka / Giuditta Guerrini / Dora Mehn / Annalisa Ciabattini / Hassan Abolhassani / David Jarrossay / Mariagrazia Uguccioni / Donata Medaglini / Qiang Pan-Hammarström / Luigi Calzolai / Daniel Fernandez / Fausto Baldanti / Alessandra Franzetti-Pellanda / Christian Garzoni / Radislav Sedlacek / Daniel Ruzek / Luca Varani / Andrea Cavalli / Christopher O Barnes / Davide F Robbiani / ![]() ![]() ![]() ![]() ![]() ![]() Abstract: Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution ...Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four , including the nine human coronaviruses, through recognition of a conserved motif that includes the S2' site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with , including SARS-CoV-2 variants. ONE SENTENCE SUMMARY: Broadly cross-reactive antibodies that protect from SARS-CoV-2 variants are revealed by virus coldspot-driven discovery. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 252.7 KB | Display | ![]() |
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PDB format | ![]() | 161.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 494.3 KB | Display | ![]() |
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Full document | ![]() | 504 KB | Display | |
Data in XML | ![]() | 42.5 KB | Display | |
Data in CIF | ![]() | 62.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8d48C ![]() 4gxuS ![]() 6fg1S S: Starting model for refinement C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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2 | ![]()
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Unit cell |
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Components
-Protein/peptide , 1 types, 2 molecules CD
#3: Protein/peptide | Mass: 2267.600 Da / Num. of mol.: 2 / Source method: obtained synthetically Source: (synth.) ![]() ![]() References: UniProt: P0DTC2 |
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-Antibody , 2 types, 4 molecules LAHB
#1: Antibody | Mass: 23236.789 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Antibody | Mass: 26159.256 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Non-polymers , 4 types, 760 molecules ![](data/chem/img/PEG.gif)
![](data/chem/img/EDO.gif)
![](data/chem/img/PO4.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/EDO.gif)
![](data/chem/img/PO4.gif)
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#4: Chemical | #5: Chemical | ChemComp-EDO / | #6: Chemical | ChemComp-PO4 / #7: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.71 Å3/Da / Density % sol: 54.65 % |
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Crystal grow | Temperature: 289 K / Method: vapor diffusion, sitting drop / pH: 4.8 Details: 0.2 M Potassium phosphate monobasic, 20% w/v Polyethylene glycol 3350 |
-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: Apr 1, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 |
Reflection | Resolution: 2→37.9 Å / Num. obs: 73148 / % possible obs: 97.9 % / Redundancy: 3 % / Biso Wilson estimate: 26.71 Å2 / CC1/2: 0.988 / Rmerge(I) obs: 0.117 / Net I/σ(I): 6.1 |
Reflection shell | Resolution: 2→2.04 Å / Redundancy: 3 % / Rmerge(I) obs: 0.996 / Mean I/σ(I) obs: 1.5 / Num. unique obs: 4545 / CC1/2: 0.372 / % possible all: 98.8 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4GXU, 6FG1 Resolution: 2→37.89 Å / SU ML: 0.2588 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 23.8159 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 31.33 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2→37.89 Å
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Refine LS restraints |
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LS refinement shell |
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