+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37835 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | XBB.1.5.70 spike protein in complex with ACE2 | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | SARS-CoV-2 / XBB.1.5.70 / ACE2 / spike protein / VIRAL PROTEIN | |||||||||
Function / homology | Function and homology information positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / positive regulation of gap junction assembly / tryptophan transport / regulation of cardiac conduction / regulation of vasoconstriction ...positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / positive regulation of gap junction assembly / tryptophan transport / regulation of cardiac conduction / regulation of vasoconstriction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / carboxypeptidase activity / negative regulation of signaling receptor activity / Attachment and Entry / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / brush border membrane / regulation of transmembrane transporter activity / cilium / negative regulation of ERK1 and ERK2 cascade / positive regulation of reactive oxygen species metabolic process / metallopeptidase activity / endocytic vesicle membrane / regulation of cell population proliferation / virus receptor activity / regulation of inflammatory response / endopeptidase activity / 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 / Potential therapeutics for SARS / 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 / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / 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 / symbiont entry into host cell / apical plasma membrane / membrane raft / endoplasmic reticulum lumen / 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 / cell surface / extracellular space / extracellular exosome / zinc ion binding / extracellular region / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.64 Å | |||||||||
Authors | Feng LL | |||||||||
Funding support | 1 items
| |||||||||
Citation | Journal: PLoS Pathog / Year: 2023 Title: Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455-456 synergistically enhances antibody evasion and ACE2 binding. Authors: Fanchong Jian / Leilei Feng / Sijie Yang / Yuanling Yu / Lei Wang / Weiliang Song / Ayijiang Yisimayi / Xiaosu Chen / Yanli Xu / Peng Wang / Lingling Yu / Jing Wang / Lu Liu / Xiao Niu / ...Authors: Fanchong Jian / Leilei Feng / Sijie Yang / Yuanling Yu / Lei Wang / Weiliang Song / Ayijiang Yisimayi / Xiaosu Chen / Yanli Xu / Peng Wang / Lingling Yu / Jing Wang / Lu Liu / Xiao Niu / Jing Wang / Tianhe Xiao / Ran An / Yao Wang / Qingqing Gu / Fei Shao / Ronghua Jin / Zhongyang Shen / Youchun Wang / Xiangxi Wang / Yunlong Cao / Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain (RBD) L455F and F456L is observed, resulting in variants with substantial growth advantages, such as EG.5, FL.1.5.1, XBB.1.5.70, and HK.3. Here, we show that neutralizing antibody (NAb) evasion drives the convergent evolution of F456L, while the epistatic shift caused by F456L enables the subsequent convergence of L455F through ACE2 binding enhancement and further immune evasion. L455F and F456L evade RBD-targeting Class 1 public NAbs, reducing the neutralization efficacy of XBB breakthrough infection (BTI) and reinfection convalescent plasma. Importantly, L455F single substitution significantly dampens receptor binding; however, the combination of L455F and F456L forms an adjacent residue flipping, which leads to enhanced NAbs resistance and ACE2 binding affinity. The perturbed receptor-binding mode leads to the exceptional ACE2 binding and NAb evasion, as revealed by structural analyses. Our results indicate the evolution flexibility contributed by epistasis cannot be underestimated, and the evolution potential of SARS-CoV-2 RBD remains high. | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_37835.map.gz | 167.8 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-37835-v30.xml emd-37835.xml | 17.6 KB 17.6 KB | Display Display | EMDB header |
Images | emd_37835.png | 28.9 KB | ||
Filedesc metadata | emd-37835.cif.gz | 6.7 KB | ||
Others | emd_37835_half_map_1.map.gz emd_37835_half_map_2.map.gz | 165.2 MB 165.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37835 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37835 | HTTPS FTP |
-Validation report
Summary document | emd_37835_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_37835_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_37835_validation.xml.gz | 15 KB | Display | |
Data in CIF | emd_37835_validation.cif.gz | 17.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37835 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37835 | HTTPS FTP |
-Related structure data
Related structure data | 8wtjMC 8wrhC 8wrlC 8wrmC 8wroC 8wtdC 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_37835.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #2
File | emd_37835_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_37835_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : XBB.1.5.70 spike protein in complex with hACE2
Entire | Name: XBB.1.5.70 spike protein in complex with hACE2 |
---|---|
Components |
|
-Supramolecule #1: XBB.1.5.70 spike protein in complex with hACE2
Supramolecule | Name: XBB.1.5.70 spike protein in complex with hACE2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|
-Supramolecule #2: spike protein
Supramolecule | Name: spike protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: human ACE2
Supramolecule | Name: human ACE2 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
-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: 145.812438 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPA LPFNDGVYF ASTEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLD VYQKNNKSWM ESEFRVYSSA N NCTFEYVS ...String: MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPA LPFNDGVYF ASTEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLD VYQKNNKSWM ESEFRVYSSA N NCTFEYVS QPFLMDLEGK EGNFKNLREF VFKNIDGYFK IYSKHTPINL ERDLPQGFSA LEPLVDLPIG INITRFQTLL AL HRSYLTP VDSSSGWTAG AAAYYVGYLQ PRTFLLKYNE NGTITDAVDC ALDPLSETKC TLKSFTVEKG IYQTSNFRVQ PTE SIVRFP NITNLCPFHE VFNATTFASV YAWNRKRISN CVADYSVIYN FAPFFAFKCY GVSPTKLNDL CFTNVYADSF VIRG NEVSQ IAPGQTGNIA DYNYKLPDDF TGCVIAWNSN KLDSKPSGNY NYLYRFLRKS KLKPFERDIS TEIYQAGNKP CNGVA GPNC YSPLQSYGFR PTYGVGHQPY RVVVLSFELL HAPATVCGPK KSTNLVKNKC VNFNFNGLTG TGVLTESNKK FLPFQQ FGR DIADTTDAVR DPQTLEILDI TPCSFGGVSV ITPGTNTSNQ VAVLYQGVNC TEVPVAIHAD QLTPTWRVYS TGSNVFQ TR AGCLIGAEYV NNSYECDIPI GAGICASYQT QTKSHGSASS VASQSIIAYT MSLGAENSVA YSNNSIAIPT NFTISVTT E ILPVSMTKTS VDCTMYICGD STECSNLLLQ YGSFCTQLKR ALTGIAVEQD KNTQEVFAQV KQIYKTPPIK YFGGFNFSQ ILPDPSKPSK RSPIEDLLFN KVTLTDAGFI KKYGDCLGDI AARDLICAQK FNGLTVLPPL LTDEMIAQYT SALLAGTITS GWTFGAGPA LQIPFPMQMA YRFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLSSTPS ALGKLQDVVN HNAQALNTLV K QLSSKFGA ISSVLNDILS RLDPPEAEVQ IDRLITGRLQ SLQTYVTQQL IRAAEIRASA NLAATKMSEC VLGQSKRVDF CG KGYHLMS FPQSAPHGVV FLHVTYVPAQ EKNFTTAPAI CHDGKAHFPR EGVFVSNGTH WFVTQRNFYE PQIITTDNTF VSG NCDVVI GIVNNTVYDP LQPELDSFKE ELDKYFKNHT SPDVDLGDIS GINASVVNIQ KEIDRLNEVA KNLNESLIDL QELG KYEQG GRGSGYIPEA PRDGQAYVRK DGEWVLLSTF LGGSGGSYIP EAPRDGQAYV RKDGEWVLLS TFLGRSLEVL FQGPG WSHP QFEKGGGSGG GSGGSSAWSH PQFEKHHHHH HHH UniProtKB: Spike glycoprotein |
-Macromolecule #2: Processed angiotensin-converting enzyme 2
Macromolecule | Name: Processed angiotensin-converting enzyme 2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 68.804328 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: STIEEQAKTF LDKFNHEAED LFYQSSLASW NYNTNITEEN VQNMNNAGDK WSAFLKEQST LAQMYPLQEI QNLTVKLQLQ ALQQNGSSV LSEDKSKRLN TILNTMSTIY STGKVCNPDN PQECLLLEPG LNEIMANSLD YNERLWAWES WRSEVGKQLR P LYEEYVVL ...String: STIEEQAKTF LDKFNHEAED LFYQSSLASW NYNTNITEEN VQNMNNAGDK WSAFLKEQST LAQMYPLQEI QNLTVKLQLQ ALQQNGSSV LSEDKSKRLN TILNTMSTIY STGKVCNPDN PQECLLLEPG LNEIMANSLD YNERLWAWES WRSEVGKQLR P LYEEYVVL KNEMARANHY EDYGDYWRGD YEVNGVDGYD YSRGQLIEDV EHTFEEIKPL YEHLHAYVRA KLMNAYPSYI SP IGCLPAH LLGDMWGRFW TNLYSLTVPF GQKPNIDVTD AMVDQAWDAQ RIFKEAEKFF VSVGLPNMTQ GFWENSMLTD PGN VQKAVC HPTAWDLGKG DFRILMCTKV TMDDFLTAHH EMGHIQYDMA YAAQPFLLRN GANEGFHEAV GEIMSLSAAT PKHL KSIGL LSPDFQEDNE TEINFLLKQA LTIVGTLPFT YMLEKWRWMV FKGEIPKDQW MKKWWEMKRE IVGVVEPVPH DETYC DPAS LFHVSNDYSF IRYYTRTLYQ FQFQEALCQA AKHEGPLHKC DISNSTEAGQ KLFNMLRLGK SEPWTLALEN VVGAKN MNV RPLLNYFEPL FTWLKDQNKN SFVGWSTDWS P UniProtKB: Angiotensin-converting enzyme 2 |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
---|---|
Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 52.0 e/Å2 |
Electron beam | Acceleration voltage: 200 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: 1.2 µm |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
---|---|
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.64 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 64562 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |