[English] 日本語
Yorodumi- EMDB-33019: SARS-CoV-2 BA.2 variant spike protein in complex with Fab BD55-5840 -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33019 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | SARS-CoV-2 BA.2 variant spike protein in complex with Fab BD55-5840 | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
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 / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Wang X / Wang L | |||||||||
Funding support | 1 items
| |||||||||
Citation | Journal: Nature / Year: 2022 Title: BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Authors: Yunlong Cao / Ayijiang Yisimayi / Fanchong Jian / Weiliang Song / Tianhe Xiao / Lei Wang / Shuo Du / Jing Wang / Qianqian Li / Xiaosu Chen / Yuanling Yu / Peng Wang / Zhiying Zhang / Pulan ...Authors: Yunlong Cao / Ayijiang Yisimayi / Fanchong Jian / Weiliang Song / Tianhe Xiao / Lei Wang / Shuo Du / Jing Wang / Qianqian Li / Xiaosu Chen / Yuanling Yu / Peng Wang / Zhiying Zhang / Pulan Liu / Ran An / Xiaohua Hao / Yao Wang / Jing Wang / Rui Feng / Haiyan Sun / Lijuan Zhao / Wen Zhang / Dong Zhao / Jiang Zheng / Lingling Yu / Can Li / Na Zhang / Rui Wang / Xiao Niu / Sijie Yang / Xuetao Song / Yangyang Chai / Ye Hu / Yansong Shi / Linlin Zheng / Zhiqiang Li / Qingqing Gu / Fei Shao / Weijin Huang / Ronghua Jin / Zhongyang Shen / Youchun Wang / Xiangxi Wang / Junyu Xiao / Xiaoliang Sunney Xie / Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage. The receptor binding and immune- ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles, epitope distribution and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab and cilgavimab can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_33019.map.gz | 168.1 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-33019-v30.xml emd-33019.xml | 15.6 KB 15.6 KB | Display Display | EMDB header |
Images | emd_33019.png | 45.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33019 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33019 | HTTPS FTP |
-Related structure data
Related structure data | 7x6aMC 7wr8C 7wrlC 7wroC 7wrzC 7xiwC 7xixC 7xiyC 7xizC 7xnqC 7xnrC 7xnsC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_33019.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Sample components
-Entire : SARS-CoV-2 BA.2 variant spike protein in complex with Fab BD55-5840
Entire | Name: SARS-CoV-2 BA.2 variant spike protein in complex with Fab BD55-5840 |
---|---|
Components |
|
-Supramolecule #1: SARS-CoV-2 BA.2 variant spike protein in complex with Fab BD55-5840
Supramolecule | Name: SARS-CoV-2 BA.2 variant spike protein in complex with Fab BD55-5840 type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #2: SARS-CoV-2 BA.2 variant spike protein
Supramolecule | Name: SARS-CoV-2 BA.2 variant spike protein / type: complex / Chimera: Yes / ID: 2 / Parent: 1 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: Fab BD55-5840
Supramolecule | Name: Fab BD55-5840 / type: complex / Chimera: Yes / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
---|
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 141.133547 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYF ASTEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLD VYYHKNNKSW MESEFRVYSS A NNCTFEYV ...String: MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYF ASTEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLD VYYHKNNKSW MESEFRVYSS A NNCTFEYV SQPFLMDLEG KQGNFKNLRE FVFKNIDGYF KIYSKHTPIN LGRDLPQGFS ALEPLVDLPI GINITRFQTL LA LHRSYLT PGDSSSGWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPT ESIVRF PNITNLCPFD EVFNATRFAS VYAWNRKRIS NCVADYSVLY NFAPFFAFKC YGVSPTKLND LCFTNVYADS FVIR GNEVS QIAPGQTGNI ADYNYKLPDD FTGCVIAWNS NKLDSKVGGN YNYLYRLFRK SNLKPFERDI STEIYQAGNK PCNGV AGFN CYFPLRSYGF RPTYGVGHQP YRVVVLSFEL LHAPATVCGP KKSTNLVKNK CVNFNFNGLT GTGVLTESNK KFLPFQ QFG RDIADTTDAV RDPQTLEILD ITPCSFGGVS VITPGTNTSN QVAVLYQGVN CTEVPVAIHA DQLTPTWRVY STGSNVF QT RAGCLIGAEY VNNSYECDIP IGAGICASYQ TQTKSHRAAA SVASQSIIAY TMSLGAENSV AYSNNSIAIP TNFTISVT T EILPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLK RALTGIAVEQ DKNTQEVFAQ VKQIYKTPPI KYFGGFNFS QILPDPSKPS KRSPIEDLLF NKVTLADAGF IKQYGDCLGD IAARDLICAQ KFNGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGP ALQIPFPMQM AYRFNGIGVT QNVLYENQKL IANQFNSAIG KIQDSLSSTP SALGKLQDVV NHNAQALNTL V KQLSSKFG AISSVLNDIL 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 YIKWPWYIWL GFIAGLIAIV MVTIMLCCMT SCCSCLKGCC SCGSCCKFDE DDSEPVLKGV KLHYT |
-Macromolecule #2: Heavy chain of Fab BD55-5840
Macromolecule | Name: Heavy chain of Fab BD55-5840 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.136394 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: VQLAQSGSEL RKPGASVKVS CDTSGHSFTS NAIHWVRQAP GQGLEWMGWI NTDTGTPTYA QGFTGRFVFS LDTSARTAYL QISSLKADD TAVFYCARER DYSDYFFDYW GQGTLVTVSS |
-Macromolecule #3: Light chain of Fab BD55-5840
Macromolecule | Name: Light chain of Fab BD55-5840 / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.635954 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVVMTQSPAS LSVSPGERAT LSCRARASLG ISTDLAWYQQ RPGQAPRLLI YGASTRATGI PARFSGSGSG TEFTLTISSL QSEDSAVYY CQQYSNWPLT FGGGTKVEIK |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8.5 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DARK FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.0 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
---|---|
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 355445 |