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- PDB-7mkm: SARS-CoV-2 Spike RBD in complex with neutralizing Fab SARS2-38 (l... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7mkm | |||||||||
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Title | SARS-CoV-2 Spike RBD in complex with neutralizing Fab SARS2-38 (local refinement) | |||||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / Glycoprotein / Antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex / Structural Genomics / Center for Structural Genomics of Infectious Diseases / CSGID | |||||||||
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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.16 Å | |||||||||
![]() | Adams, L.J. / Fremont, D.H. / Center for Structural Genomics of Infectious Diseases (CSGID) | |||||||||
Funding support | ![]()
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![]() | ![]() Title: A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope. Authors: Laura A VanBlargan / Lucas J Adams / Zhuoming Liu / Rita E Chen / Pavlo Gilchuk / Saravanan Raju / Brittany K Smith / Haiyan Zhao / James Brett Case / Emma S Winkler / Bradley M Whitener / ...Authors: Laura A VanBlargan / Lucas J Adams / Zhuoming Liu / Rita E Chen / Pavlo Gilchuk / Saravanan Raju / Brittany K Smith / Haiyan Zhao / James Brett Case / Emma S Winkler / Bradley M Whitener / Lindsay Droit / Ishmael D Aziati / Traci L Bricker / Astha Joshi / Pei-Yong Shi / Adrian Creanga / Amarendra Pegu / Scott A Handley / David Wang / Adrianus C M Boon / James E Crowe / Sean P J Whelan / Daved H Fremont / Michael S Diamond / ![]() Abstract: With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory ...With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here, we developed a panel of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) that bound the receptor binding domain of the spike protein at distinct epitopes and blocked virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Although several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by ancestral SARS-CoV-2 strains, others induced escape variants in vivo or lost neutralizing activity against emerging strains. One mAb, SARS2-38, potently neutralized all tested SARS-CoV-2 variants of concern and protected mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engaged a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of neutralizing antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants. #1: Journal: bioRxiv / Year: 2021 Title: A potently neutralizing anti-SARS-CoV-2 antibody inhibits variants of concern by binding a highly conserved epitope. Authors: Laura VanBlargan / Lucas Adams / Zhuoming Liu / Rita E Chen / Pavlo Gilchuk / Saravanan Raju / Brittany Smith / Haiyan Zhao / James Brett Case / Emma S Winkler / Bradley Whitener / Lindsay ...Authors: Laura VanBlargan / Lucas Adams / Zhuoming Liu / Rita E Chen / Pavlo Gilchuk / Saravanan Raju / Brittany Smith / Haiyan Zhao / James Brett Case / Emma S Winkler / Bradley Whitener / Lindsay Droit / Ismael Aziati / Pei-Yong Shi / Adrian Creanga / Amarendra Pegu / Scott Handley / David Wang / Adrianus Boon / James E Crowe / Sean P J Whelan / Daved Fremont / Michael Diamond Abstract: With the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of ...With the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of neutralizing anti-SARS-CoV-2 mAbs that bind the receptor binding domain of the spike protein at distinct epitopes and block virus attachment to cells and its receptor, human angiotensin converting enzyme-2 (hACE2). While several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by historical SARS-CoV-2 strains, others induced escape variants in vivo and lost activity against emerging strains. We identified one mAb, SARS2-38, that potently neutralizes all SARS-CoV-2 variants of concern tested and protects mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engages a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of inhibitory antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants. | |||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 88.2 KB | Display | ![]() |
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PDB format | ![]() | 67.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 23899MC ![]() 7mklC M: map data used to model this data 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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Components
#1: Protein | Mass: 21247.758 Da / Num. of mol.: 1 / Fragment: receptor binding domain (UNP residues 333-520) Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: S, 2 / Cell line (production host): Expi293F / Production host: ![]() |
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#2: Antibody | Mass: 12490.882 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#3: Antibody | Mass: 11419.787 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#4: Sugar | ChemComp-NAG / |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: SARS-CoV-2 spike bound by SARS2-38 antibody Fab / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: cryoSPARC / Version: 3.1.0 / Category: 3D reconstruction | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.16 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 272007 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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