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Yorodumi- EMDB-65168: Cryo-EM structure of SARS-CoV-2 XBB.1.5 S trimer in the early fus... -
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Basic information
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| Title | Cryo-EM structure of SARS-CoV-2 XBB.1.5 S trimer in the early fusion intermediate conformation (E-FIC) complexed with ACE2 and 76E1-Fab | |||||||||
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Keywords | Spike / ACE2 / and 76E1-Fab complex / VIRAL PROTEIN / HYDROLASE / VIRAL PROTEIN-HYDROLASE complex | |||||||||
| Function / homology | Function and homology informationpositive 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 / positive regulation of gap junction assembly / tryptophan transport / regulation of systemic arterial blood pressure by renin-angiotensin / maternal process involved in female pregnancy / regulation of cardiac conduction ...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 / positive regulation of gap junction assembly / tryptophan transport / regulation of systemic arterial blood pressure by renin-angiotensin / maternal process involved in female pregnancy / regulation of cardiac conduction / peptidyl-dipeptidase activity / regulation of vasoconstriction / transporter activator activity / Metabolism of Angiotensinogen to Angiotensins / carboxypeptidase activity / angiotensin maturation / viral life cycle / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / metallocarboxypeptidase activity / positive regulation of cardiac muscle contraction / regulation of cytokine production / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / brush border membrane / 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 / symbiont-mediated disruption of host tissue / Maturation of spike protein / Translation of Structural Proteins / Virion Assembly and Release / endopeptidase activity / host cell surface / host extracellular region / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / Potential therapeutics for SARS / positive regulation of viral entry into host cell / membrane fusion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / entry receptor-mediated virion attachment to host cell / receptor-mediated virion attachment to host cell / apical plasma membrane / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / cilium / endocytosis involved in viral entry into host cell / membrane raft / endoplasmic reticulum lumen / receptor ligand activity / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / symbiont entry into host cell / virion attachment to host cell / host cell plasma membrane / SARS-CoV-2 activates/modulates innate and adaptive immune responses / virion membrane / cell surface / negative regulation of transcription by RNA polymerase II / : / extracellular exosome / extracellular region / zinc ion binding / membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||
| Biological species | ![]() Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 5.65 Å | |||||||||
Authors | Liu ZM / Bao ZH / Sun XY / Sun L | |||||||||
| Funding support | China, 1 items
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Citation | Journal: Nature / Year: 2026Title: Steric hindrance of antibody binding in an Omicron spike fusion intermediate. Authors: Zhiheng Bao / Zhimin Liu / Zhaoyong Zhang / Xuanjia Wang / Xiaohui Jin / Jiaxiu Bai / Hanwen Ma / Yaxin Li / Chunyan Yi / Zhiyang Ling / Zhong Huang / Lu Zhang / Zhenguo Chen / Youhua Xie / ...Authors: Zhiheng Bao / Zhimin Liu / Zhaoyong Zhang / Xuanjia Wang / Xiaohui Jin / Jiaxiu Bai / Hanwen Ma / Yaxin Li / Chunyan Yi / Zhiyang Ling / Zhong Huang / Lu Zhang / Zhenguo Chen / Youhua Xie / Yanqun Wang / Lei Sun / Xiaoyu Sun / ![]() Abstract: Understanding conformational changes of the coronavirus spike protein is critical for developing broad-spectrum therapies. The pan-coronavirus epitope spike residues 815-825 (centred on the S2' site) ...Understanding conformational changes of the coronavirus spike protein is critical for developing broad-spectrum therapies. The pan-coronavirus epitope spike residues 815-825 (centred on the S2' site) are buried in the prefusion spike but are transiently exposed upon ACE2 binding. Here, using integrated functional and structural analyses, we demonstrate that 76E1, an antibody targeting spike residues 815-825, specifically recognizes an open early fusion intermediate conformation in which this epitope adopts a helical conformation, designated the S2'-helix. SARS-CoV-2 Omicron variants evade such antibodies via steric hindrance resulting from S2'-helix shifts and restricted S1-ACE2 distancing in the early fusion intermediate conformation, together with increased reliance on cathepsin-mediated entry that impairs 76E1 inhibition of S2' cleavage. The H655Y mutation is central to this evasion. Antibody size directly affects its access to the S2'-helix. Crucially, antibody size minimization reversed the evasion mechanisms and significantly enhanced neutralizing activity against authentic Omicron variants and other human coronaviruses, including SARS-CoV-1 and HCoV-229E. These findings establish small-molecule targeting of the S2'-helix as a strategy for pan-coronavirus therapies. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_65168.map.gz | 123 MB | EMDB map data format | |
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| Header (meta data) | emd-65168-v30.xml emd-65168.xml | 27.6 KB 27.6 KB | Display Display | EMDB header |
| Images | emd_65168.png | 70.5 KB | ||
| Filedesc metadata | emd-65168.cif.gz | 8.1 KB | ||
| Others | emd_65168_additional_1.map.gz emd_65168_half_map_1.map.gz emd_65168_half_map_2.map.gz | 118 MB 226.4 MB 226.4 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-65168 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-65168 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9vltMC ![]() 9ld2C ![]() 9ldjC ![]() 9vlsC C: citing same article ( M: atomic model generated by this map |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_65168.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.932 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Additional map: #1
| File | emd_65168_additional_1.map | ||||||||||||
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-Half map: #2
| File | emd_65168_half_map_1.map | ||||||||||||
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-Half map: #1
| File | emd_65168_half_map_2.map | ||||||||||||
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Sample components
-Entire : the XBB.1.5 E-FIC-76E1 structure
| Entire | Name: the XBB.1.5 E-FIC-76E1 structure |
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| Components |
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-Supramolecule #1: the XBB.1.5 E-FIC-76E1 structure
| Supramolecule | Name: the XBB.1.5 E-FIC-76E1 structure / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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| Source (natural) | Organism: ![]() |
-Macromolecule #1: Spike glycoprotein
| Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 142.39275 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 NYLYRLFRKS 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 QTKSHRRARS VASQSIIAYT MSLGAENSVA YSNNSIAIPT NFTISVTT E ILPVSMTKTS VDCTMYICGD STECSNLLLQ YGSFCTQLKR ALTGIAVEQD KNTQEVFAQV KQIYKTPPIK YFGGFNFSQ ILPDPSKPSK RSFIEDLLFN KVTLADAGFI KQYGDCLGDI AARDLICAQK FNGLTVLPPL LTDEMIAQYT SALLAGTITS GWTFGAGAA LQIPFAMQMA YRFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLSSTAS ALGKLQDVVN HNAQALNTLV K QLSSKFGA ISSVLNDILS RLDKVEAEVQ 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 SGYIPEAPRD GQAYVRKDGE WVFLSTFLSG LEVLFQGPGG WSHPQFEKGG GSGGGSGGSA WSHPQFEKGG SHHHH HHHH UniProtKB: Spike glycoprotein |
-Macromolecule #2: Angiotensin-converting enzyme 2
| Macromolecule | Name: Angiotensin-converting enzyme 2 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO / EC number: angiotensin-converting enzyme 2 |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 72.989047 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: MSSSSWLLLS LVAVTAAQST IEEQAKTFLD KFNHEAEDLF YQSSLASWNY NTNITEENVQ NMNNAGDKWS AFLKEQSTLA QMYPLQEIQ NLTVKLQLQA LQQNGSSVLS EDKSKRLNTI LNTMSTIYST GKVCNPDNPQ ECLLLEPGLN EIMANSLDYN E RLWAWESW ...String: MSSSSWLLLS LVAVTAAQST IEEQAKTFLD KFNHEAEDLF YQSSLASWNY NTNITEENVQ NMNNAGDKWS AFLKEQSTLA QMYPLQEIQ NLTVKLQLQA LQQNGSSVLS EDKSKRLNTI LNTMSTIYST GKVCNPDNPQ ECLLLEPGLN EIMANSLDYN E RLWAWESW RSEVGKQLRP LYEEYVVLKN EMARANHYED YGDYWRGDYE VNGVDGYDYS RGQLIEDVEH TFEEIKPLYE HL HAYVRAK LMNAYPSYIS PIGCLPAHLL GDMWGRFWTN LYSLTVPFGQ KPNIDVTDAM VDQAWDAQRI FKEAEKFFVS VGL PNMTQG FWENSMLTDP GNVQKAVCHP TAWDLGKGDF RILMCTKVTM DDFLTAHHEM GHIQYDMAYA AQPFLLRNGA NEGF HEAVG EIMSLSAATP KHLKSIGLLS PDFQEDNETE INFLLKQALT IVGTLPFTYM LEKWRWMVFK GEIPKDQWMK KWWEM KREI VGVVEPVPHD ETYCDPASLF HVSNDYSFIR YYTRTLYQFQ FQEALCQAAK HEGPLHKCDI SNSTEAGQKL FNMLRL GKS EPWTLALENV VGAKNMNVRP LLNYFEPLFT WLKDQNKNSF VGWSTDWSPY ADLEVLFQGP HHHHHHHH UniProtKB: Angiotensin-converting enzyme 2 |
-Macromolecule #3: heavy chain of 76E1 Fab
| Macromolecule | Name: heavy chain of 76E1 Fab / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 23.378164 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: EVQLVESGGG VVQPGGSLRL SCEASGFSFK DYGMHWIRQT PGKGLEWISR ISGDTRGTSY VDSVKGRFIV SRDNSRNSLF LQMNSLRSE DTALYYCAAL VIVAAGDDFD LWGQGTVVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT ...String: EVQLVESGGG VVQPGGSLRL SCEASGFSFK DYGMHWIRQT PGKGLEWISR ISGDTRGTSY VDSVKGRFIV SRDNSRNSLF LQMNSLRSE DTALYYCAAL VIVAAGDDFD LWGQGTVVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKK VEP |
-Macromolecule #4: light chain of 76E1 Fab
| Macromolecule | Name: light chain of 76E1 Fab / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 22.949475 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: QSALTQPLSV SGSPGQSVTI SCTGSSSDIG SYNFVSWYRQ YPGKAPKVMI YEVNKRPSGV PVRFSGSKSG NTASLTVSGL QHEDEADYY CCSYGGRNNL IFGGGTKLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP ...String: QSALTQPLSV SGSPGQSVTI SCTGSSSDIG SYNFVSWYRQ YPGKAPKVMI YEVNKRPSGV PVRFSGSKSG NTASLTVSGL QHEDEADYY CCSYGGRNNL IFGGGTKLTV LGQPKAAPSV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADSSPV K AGVETTTP SKQSNNKYAA SSYLSLTPEQ WKSHRSYSCQ VTHEGSTVEK TVAPTECS |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
| Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 33 / Formula: NAG |
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| Molecular weight | Theoretical: 221.208 Da |
| Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 8 |
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| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
| Microscope | TFS KRIOS |
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| 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: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Keywords
Homo sapiens (human)
Authors
China, 1 items
Citation













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Processing
FIELD EMISSION GUN
