[English] 日本語
![](img/lk-miru.gif)
- EMDB-37162: Structure of SARS-CoV-2 Omicron BA.1 Spike complexed with antibod... -
+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of SARS-CoV-2 Omicron BA.1 Spike complexed with antibody PW5-570 | |||||||||
![]() | ||||||||||
![]() |
| |||||||||
![]() | Antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM 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 / symbiont-mediated suppression of host innate immune response / 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 | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.78 Å | |||||||||
![]() | Sun L / Mao Q / Wang Y | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination. Authors: Xiaoyu Zhao / Tianyi Qiu / Xiner Huang / Qiyu Mao / Yajie Wang / Rui Qiao / Jiayan Li / Tiantian Mao / Yuan Wang / Yewei Cun / Caicui Wang / Cuiting Luo / Chaemin Yoon / Xun Wang / Chen Li / ...Authors: Xiaoyu Zhao / Tianyi Qiu / Xiner Huang / Qiyu Mao / Yajie Wang / Rui Qiao / Jiayan Li / Tiantian Mao / Yuan Wang / Yewei Cun / Caicui Wang / Cuiting Luo / Chaemin Yoon / Xun Wang / Chen Li / Yuchen Cui / Chaoyue Zhao / Minghui Li / Yanjia Chen / Guonan Cai / Wenye Geng / Zixin Hu / Jinglei Cao / Wenhong Zhang / Zhiwei Cao / Hin Chu / Lei Sun / Pengfei Wang / ![]() Abstract: The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the ...The current SARS-CoV-2 variants strikingly evade all authorized monoclonal antibodies and threaten the efficacy of serum-neutralizing activity elicited by vaccination or prior infection, urging the need to develop antivirals against SARS-CoV-2 and related sarbecoviruses. Here, we identified both potent and broadly neutralizing antibodies from a five-dose vaccinated donor who exhibited cross-reactive serum-neutralizing activity against diverse coronaviruses. Through single B-cell sorting and sequencing followed by a tailor-made computational pipeline, we successfully selected 86 antibodies with potential cross-neutralizing ability from 684 antibody sequences. Among them, PW5-570 potently neutralized all SARS-CoV-2 variants that arose prior to Omicron BA.5, and the other three could broadly neutralize all current SARS-CoV-2 variants of concern, SARS-CoV and their related sarbecoviruses (Pangolin-GD, RaTG13, WIV-1, and SHC014). Cryo-EM analysis demonstrates that these antibodies have diverse neutralization mechanisms, such as disassembling spike trimers, or binding to RBM or SD1 to affect ACE2 binding. In addition, prophylactic administration of these antibodies significantly protects nasal turbinate and lung infections against BA.1, XBB.1, and SARS-CoV viral challenge in golden Syrian hamsters, respectively. Importantly, post-exposure treatment with PW5-5 and PW5-535 also markedly protects against XBB.1 challenge in these models. This study reveals the potential utility of computational process to assist screening cross-reactive antibodies, as well as the potency of vaccine-induced broadly neutralizing antibodies against current SARS-CoV-2 variants and related sarbecoviruses, offering promising avenues for the development of broad therapeutic antibody drugs. | |||||||||
History |
|
-
Structure visualization
-
Downloads & links
-EMDB archive
Map data | ![]() | |||
---|---|---|---|---|
Header (meta data) | ![]() | |||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8keoMC ![]() 37139 ![]() 37143 ![]() 37144 ![]() 37145 ![]() 37160 ![]() 37161 ![]() 37163 ![]() 37164 ![]() 37165 ![]() 8kdmC ![]() 8kdrC ![]() 8kdsC ![]() 8kdtC ![]() 8kejC ![]() 8kekC ![]() 8kepC ![]() 8keqC ![]() 8kerC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.19 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-
Sample components
-Entire : BA.1 spike protein (S) trimer in complex with broadly neutralizin...
Entire | Name: BA.1 spike protein (S) trimer in complex with broadly neutralizing antibody PW5-570 |
---|---|
Components |
|
-Supramolecule #1: BA.1 spike protein (S) trimer in complex with broadly neutralizin...
Supramolecule | Name: BA.1 spike protein (S) trimer in complex with broadly neutralizing antibody PW5-570 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Details: BA.1 spike / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 142.718297 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ ...String: MFVFLVLLPL VSSQCVNLTT RTQLPPAYTN SFTRGVYYPD KVFRSSVLHS TQDLFLPFFS NVTWFHVISG TNGTKRFDNP VLPFNDGVY FASIEKSNII RGWIFGTTLD SKTQSLLIVN NATNVVIKVC EFQFCNDPFL DHKNNKSWME SEFRVYSSAN N CTFEYVSQ PFLMDLEGKQ GNFKNLREFV FKNIDGYFKI YSKHTPIIVR EPEDLPQGFS ALEPLVDLPI GINITRFQTL LA LHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPT ESIVRF PNITNLCPFD EVFNATRFAS VYAWNRKRIS NCVADYSVLY NLAPFFTFKC YGVSPTKLND LCFTNVYADS FVIR GDEVR QIAPGQTGNI ADYNYKLPDD FTGCVIAWNS NKLDSKVSGN YNYLYRLFRK SNLKPFERDI STEIYQAGNK PCNGV AGFN CYFPLRSYSF RPTYGVGHQP YRVVVLSFEL LHAPATVCGP KKSTNLVKNK CVNFNFNGLK GTGVLTESNK KFLPFQ QFG RDIADTTDAV RDPQTLEILD ITPCSFGGVS VITPGTNTSN QVAVLYQGVN CTEVPVAIHA DQLTPTWRVY STGSNVF QT RAGCLIGAEY VNNSYECDIP IGAGICASYQ TQTKSHRRAR SVASQSIIAY TMSLGAENSV AYSNNSIAIP TNFTISVT T EILPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLK RALTGIAVEQ DKNTQEVFAQ VKQIYKTPPI KYFGGFNFS QILPDPSKPS KRSFIEDLLF NKVTLADAGF IKQYGDCLGD IAARDLICAQ KFKGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGA ALQIPFAMQM AYRFNGIGVT QNVLYENQKL IANQFNSAIG KIQDSLSSTA SALGKLQDVV NHNAQALNTL V KQLSSKFG AISSVLNDIF SRLDPPEAEV QIDRLITGRL QSLQTYVTQQ LIRAAEIRAS ANLAATKMSE CVLGQSKRVD FC GKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVS GNCDVV IGIVNNTVYD PLQPELDSFK EELDKYFKNH TSPDVDLGDI SGINASVVNI QKEIDRLNEV AKNLNESLID LQEL GKYEQ GSGYIPEAPR DGQAYVRKDG EWVFLSTFLS GLEVLFQGPG GWSHPQFEKG GGSGGGSGGS AWSHPQFEKG GSHHH HHHH H UniProtKB: Spike glycoprotein |
-Macromolecule #2: PW5-570 heavy chain
Macromolecule | Name: PW5-570 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 49.548699 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QMQLVQSGPE VRKPGTSVKV SCRASVFSFD TSAVQWVRQA RGQPLEWIGW IVFGSSNTDY AQKFRDRVTI TGDMSTGTAY MELSSLRSE DTAVYYCAAP HCNRTNCHDG FDIWGQGTVV TVSSTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT ...String: QMQLVQSGPE VRKPGTSVKV SCRASVFSFD TSAVQWVRQA RGQPLEWIGW IVFGSSNTDY AQKFRDRVTI TGDMSTGTAY MELSSLRSE DTAVYYCAAP HCNRTNCHDG FDIWGQGTVV TVSSTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKK VEPKSCDKTH TCPPCPAPEL LG GPSVFLF PPKPKDTLMI SRTPEVTCVV VDVSHEDPEV KFNWYVDGVE VHNAKTKPRE EQYNSTYRVV SVLTVLHQDW LNG KEYKCK VSNKALPAPI EKTISKAKGQ PREPQVYTLP PSRDELTKNQ VSLTCLVKGF YPSDIAVEWE SNGQPENNYK TTPP VLDSD GSFFLYSKLT VDKSRWQQGN VFSCSVLHEA LHSHYTQKSL SLSPGK |
-Macromolecule #3: PW5-570 light chain
Macromolecule | Name: PW5-570 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.802461 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EIVLTQSPGT LSLSPGERAT LSCRASQSVR SGYLGWYQQK PGQAPRLLIY GAYNRATGIP DRFRGSGSGT DFTLTISRLE PEDFVVYYC QQYDRSPWTF GQGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: EIVLTQSPGT LSLSPGERAT LSCRASQSVR SGYLGWYQQK PGQAPRLLIY GAYNRATGIP DRFRGSGSGT DFTLTISRLE PEDFVVYYC QQYDRSPWTF GQGTKVEIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
-
Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.78 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 439708 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |