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Yorodumi- PDB-7laa: Structure of SARS-CoV-2 S protein in complex with Receptor Bindin... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7laa | ||||||
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Title | Structure of SARS-CoV-2 S protein in complex with Receptor Binding Domain antibody DH1041 | ||||||
Components |
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Keywords | VIRAL PROTEIN / IMMUNE SYSTEM / RBD antibody / DH1041 / SARS / COVID-19 / SARS-CoV-2 2P S ectodomain | ||||||
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 / 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 | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.42 Å | ||||||
Authors | Manne, K. / Acharya, P. | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell / Year: 2021 Title: In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies. Authors: Dapeng Li / Robert J Edwards / Kartik Manne / David R Martinez / Alexandra Schäfer / S Munir Alam / Kevin Wiehe / Xiaozhi Lu / Robert Parks / Laura L Sutherland / Thomas H Oguin / Charlene ...Authors: Dapeng Li / Robert J Edwards / Kartik Manne / David R Martinez / Alexandra Schäfer / S Munir Alam / Kevin Wiehe / Xiaozhi Lu / Robert Parks / Laura L Sutherland / Thomas H Oguin / Charlene McDanal / Lautaro G Perez / Katayoun Mansouri / Sophie M C Gobeil / Katarzyna Janowska / Victoria Stalls / Megan Kopp / Fangping Cai / Esther Lee / Andrew Foulger / Giovanna E Hernandez / Aja Sanzone / Kedamawit Tilahun / Chuancang Jiang / Longping V Tse / Kevin W Bock / Mahnaz Minai / Bianca M Nagata / Kenneth Cronin / Victoria Gee-Lai / Margaret Deyton / Maggie Barr / Tarra Von Holle / Andrew N Macintyre / Erica Stover / Jared Feldman / Blake M Hauser / Timothy M Caradonna / Trevor D Scobey / Wes Rountree / Yunfei Wang / M Anthony Moody / Derek W Cain / C Todd DeMarco / Thomas N Denny / Christopher W Woods / Elizabeth W Petzold / Aaron G Schmidt / I-Ting Teng / Tongqing Zhou / Peter D Kwong / John R Mascola / Barney S Graham / Ian N Moore / Robert Seder / Hanne Andersen / Mark G Lewis / David C Montefiori / Gregory D Sempowski / Ralph S Baric / Priyamvada Acharya / Barton F Haynes / Kevin O Saunders / Abstract: SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor- ...SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques. #1: Journal: Biorxiv / Year: 2021 Title: In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies Authors: Li, D. / Edwards, R.J. / Manne, K. / Martinez, D.R. / Schafer, A. / Alam, S.M. / Wiehe, K. / Lu, X. / Parks, R. / Sutherland, L.L. / Oguin, T.H. / McDanal, C. / Perez, L.G. / Mansouri, K. / ...Authors: Li, D. / Edwards, R.J. / Manne, K. / Martinez, D.R. / Schafer, A. / Alam, S.M. / Wiehe, K. / Lu, X. / Parks, R. / Sutherland, L.L. / Oguin, T.H. / McDanal, C. / Perez, L.G. / Mansouri, K. / Gobeil, S.M.C. / Janowska, K. / Stalls, V. / Kopp, M. / Cai, F. / Lee, E. / Foulger, A. / Hernandez, G.E. / Sanzone, A. / Tilahun, K. / Jiang, C. / Tse, L.V. / Bock, K.W. / Minai, M. / Nagata, B.M. / Cronin, K. / Gee-Lai, V. / Deyton, M. / Barr, M. / Von Holle, T. / Macintyre, A.N. / Stover, E. / Feldman, J. / Hauser, B.M. / Caradonna, T.M. / Scobey, T.D. / Moody, M.A. / Cain, D.W. / DeMarco, C.T. / Denny, T.N. / Woods, C.W. / Petzold, E.W. / Schmidt, A.G. / Teng, I.T. / Zhou, T. / Kwong, P.D. / Mascola, J.R. / Graham, B.S. / Moore, I.N. / Seder, R. / Andersen, H. / Lewis, M.G. / Montefiori, D.C. / Sempowski, G.D. / Baric, R.S. / Acharya, P. / Haynes, B.F. / Saunders, K.O. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7laa.cif.gz | 984.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7laa.ent.gz | 839.3 KB | Display | PDB format |
PDBx/mmJSON format | 7laa.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/la/7laa ftp://data.pdbj.org/pub/pdb/validation_reports/la/7laa | HTTPS FTP |
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-Related structure data
Related structure data | 23246MC 7labC 7lcnC 7ld1C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 3 molecules ABC
#1: Protein | Mass: 124125.477 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 |
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-Antibody , 2 types, 2 molecules HL
#2: Antibody | Mass: 24125.973 Da / Num. of mol.: 1 / Fragment: Receptor Binding Domain 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: 23043.367 Da / Num. of mol.: 1 / Fragment: Receptor Binding Domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
-Sugars , 3 types, 34 molecules
#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #6: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Temperature (max): 93.15 K / Temperature (min): 93.15 K |
Image recording | Electron dose: 65.94 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | |||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.42 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 151384 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL | |||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6VXX | |||||||||||||||||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | |||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 16.13 Å2 | |||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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