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- PDB-7dk7: S-2H2-F3b structure, three RBDs are up and each RBD binds with a ... -

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Basic information

Entry
Database: PDB / ID: 7dk7
TitleS-2H2-F3b structure, three RBDs are up and each RBD binds with a 2H2 Fab.
Components
  • Spike glycoprotein
  • The heavy chain fragment of 2H2 Fab
  • The light chain fragment of 2H2 Fab
KeywordsVIRAL PROTEIN
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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / 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 / 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
Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, betacoronavirus / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike glycoprotein, betacoronavirus / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2 / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal
Similarity search - Domain/homology
Biological speciesSevere acute respiratory syndrome coronavirus 2
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 9.7 Å
AuthorsCong, Y. / Wang, Y.F.
Funding support China, 1items
OrganizationGrant numberCountry
Chinese Academy of SciencesXDB29040300 China
CitationJournal: Nat Commun / Year: 2021
Title: Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections.
Authors: Chao Zhang / Yifan Wang / Yuanfei Zhu / Caixuan Liu / Chenjian Gu / Shiqi Xu / Yalei Wang / Yu Zhou / Yanxing Wang / Wenyu Han / Xiaoyu Hong / Yong Yang / Xueyang Zhang / Tingfeng Wang / ...Authors: Chao Zhang / Yifan Wang / Yuanfei Zhu / Caixuan Liu / Chenjian Gu / Shiqi Xu / Yalei Wang / Yu Zhou / Yanxing Wang / Wenyu Han / Xiaoyu Hong / Yong Yang / Xueyang Zhang / Tingfeng Wang / Cong Xu / Qin Hong / Shutian Wang / Qiaoyu Zhao / Weihua Qiao / Jinkai Zang / Liangliang Kong / Fangfang Wang / Haikun Wang / Di Qu / Dimitri Lavillette / Hong Tang / Qiang Deng / Youhua Xie / Yao Cong / Zhong Huang /
Abstract: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for ...The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.
History
DepositionNov 23, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 2, 2020Provider: repository / Type: Initial release
Revision 1.1Jan 27, 2021Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Mar 10, 2021Group: Structure summary / Category: entity / entity_name_com / Item: _entity.pdbx_description / _entity_name_com.name

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Structure visualization

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Assembly

Deposited unit
e: The heavy chain fragment of 2H2 Fab
f: The light chain fragment of 2H2 Fab
A: Spike glycoprotein
B: Spike glycoprotein
a: The heavy chain fragment of 2H2 Fab
b: The light chain fragment of 2H2 Fab
c: The heavy chain fragment of 2H2 Fab
d: The light chain fragment of 2H2 Fab
C: Spike glycoprotein


Theoretical massNumber of molelcules
Total (without water)560,5619
Polymers560,5619
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: assay for oligomerization
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area41850 Å2
ΔGint-216 kcal/mol
Surface area184150 Å2

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Components

#1: Antibody The heavy chain fragment of 2H2 Fab


Mass: 22822.611 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Strain: Balb/C
#2: Antibody The light chain fragment of 2H2 Fab


Mass: 23975.307 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) / Strain: Balb/C
#3: Protein Spike glycoprotein / S glycoprotein / E2 / Peplomer protein / SARS-CoV-2 S protein


Mass: 140055.906 Da /