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Yorodumi- EMDB-64078: Cryo-EM structure of SARS-CoV-2 KP.2 spike in complex with ACE2 -
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Basic information
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| Title | Cryo-EM structure of SARS-CoV-2 KP.2 spike in complex with ACE2 | |||||||||
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Keywords | Spike and ACE2 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 / transporter activator activity / regulation of vasoconstriction / Metabolism of Angiotensinogen to Angiotensins / carboxypeptidase activity / angiotensin maturation / Attachment and Entry / viral life cycle / receptor-mediated endocytosis of virus by host cell / 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 / endopeptidase activity / Induction of Cell-Cell Fusion / Potential therapeutics for SARS / membrane fusion / Attachment and Entry / entry receptor-mediated virion attachment to host cell / receptor-mediated virion attachment to host cell / apical plasma membrane / cilium / membrane raft / endoplasmic reticulum lumen / symbiont entry into host cell / 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: 2.27 Å | |||||||||
Authors | Jin XH / Sun L | |||||||||
| Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2025Title: Pathogenicity, virological features, and immune evasion of SARS-CoV-2 JN.1-derived variants including JN.1.7, KP.2, KP.3, and KP.3.1.1. Authors: Jialu Shi / Xiaoyu Zhao / Xiaohui Jin / Jiayan Li / Yuanchen Liu / Huan Liu / Ye-Fan Hu / Zhe Chen / Yuxin Xiao / Lei Wang / Yajie Wang / Yixin He / Yue Chai / Bingjie Hu / Huiping Shuai / ...Authors: Jialu Shi / Xiaoyu Zhao / Xiaohui Jin / Jiayan Li / Yuanchen Liu / Huan Liu / Ye-Fan Hu / Zhe Chen / Yuxin Xiao / Lei Wang / Yajie Wang / Yixin He / Yue Chai / Bingjie Hu / Huiping Shuai / Yang Wang / Xiangnan Li / Shujun Jiang / Yanliang Zhang / Xiaojuan Zhang / Wan-Mui Chan / Lin-Lei Chen / Jian-Piao Cai / Baokun Sui / Honglei Zhang / Dong Yang / Longchao Zhu / Shuofeng Yuan / Jie Zhou / Jian-Dong Huang / Kwok-Yung Yuen / Kelvin Kai-Wang To / Jasper Fuk-Woo Chan / Bao-Zhong Zhang / Qiao Wang / Maozhou He / Lei Sun / Pengfei Wang / Hin Chu / ![]() Abstract: KP.3.1.1 became a dominant successor to JN.1 by the second half of 2024 but the intrinsic pathogenicity and virological feature of KP.3.1.1 remain incompletely understood. Here, we comprehensively ...KP.3.1.1 became a dominant successor to JN.1 by the second half of 2024 but the intrinsic pathogenicity and virological feature of KP.3.1.1 remain incompletely understood. Here, we comprehensively evaluated the pathogenesis and characteristics of KP.3.1.1 in comparison to JN.1 and other JN.1-derived variants including JN.1.7, KP.2, and KP.3. The unique S31del mutation on KP.3.1.1 spike confers further evasion to the clinically authorized mAb Pemivibart and reduces convalescent serum neutralization efficiency. Structural analysis indicates that S31del induces novel glycosylation sites that facilitates evasion of neutralizing antibodies. We further reveal that S31del significantly enhances pseudovirus entry efficiency in all evaluated cell types including the human primary nasal epithelial cells. Nevertheless, the intrinsic pathogenicity of KP.3.1.1 is similar to JN.1 and KP.3, and higher than that of JN.1.7 and KP.2 in a male hamster model. Interestingly, the increased virus infectivity conferred by S31del in KP.3.1.1 spike is counterbalanced by the NSP10 S33C mutation. Overall, our study indicates that a single spike mutation can confer both enhanced immune escape and increased viral infectivity. The opposing effects of spike and non-spike mutations highlight the complex interplay of viral genomic elements in shaping their overall fitness, and reveal the high plasticity of coronavirus evolution. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_64078.map.gz | 159.4 MB | EMDB map data format | |
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| Header (meta data) | emd-64078-v30.xml emd-64078.xml | 19.8 KB 19.8 KB | Display Display | EMDB header |
| Images | emd_64078.png | 43.5 KB | ||
| Filedesc metadata | emd-64078.cif.gz | 7.2 KB | ||
| Others | emd_64078_half_map_1.map.gz emd_64078_half_map_2.map.gz | 226.4 MB 226.4 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-64078 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-64078 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9ue7MC ![]() 9ue6C ![]() 9ujeC M: atomic model generated by this map C: citing same article ( |
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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_64078.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
-Half map: #1
| File | emd_64078_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #2
| File | emd_64078_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : KP.2 spike in complex with ACE2
| Entire | Name: KP.2 spike in complex with ACE2 |
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| Components |
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-Supramolecule #1: KP.2 spike in complex with ACE2
| Supramolecule | Name: KP.2 spike in complex with ACE2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: ![]() |
-Macromolecule #1: Angiotensin-converting enzyme 2
| Macromolecule | Name: Angiotensin-converting enzyme 2 / type: protein_or_peptide / ID: 1 / 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 #2: Spike glycoprotein
| Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 144.600156 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: MPMGSLQPLA TLYLLGMLVA SVLAQCVNLI TTTQSYTNSF TRGVYYPDKV FRSSVLHLTQ DLFLPFFSNV TWFHAISGTN GTKRFDNPV LPFNDGVYFA STEKSNIIRG WIFGTTLDSK TQSLLIVNNA TNFVIKVCEF QFCNDPFLDV YHKNNKSWME S ESGVYSSA ...String: MPMGSLQPLA TLYLLGMLVA SVLAQCVNLI TTTQSYTNSF TRGVYYPDKV FRSSVLHLTQ DLFLPFFSNV TWFHAISGTN GTKRFDNPV LPFNDGVYFA STEKSNIIRG WIFGTTLDSK TQSLLIVNNA TNFVIKVCEF QFCNDPFLDV YHKNNKSWME S ESGVYSSA NNCTFEYVSQ PFLMDLEGKQ GNFKNLREFV FKNIDGYFKI YSKHTPIIGR DFPQGFSALE PLVDLPIGIN IT RFQTLLA LNRSYLTPGD SSSGWTAGAA DYYVGYLQPR TFLLKYNENG TITDAVDCAL DPLSETKCTL KSFTVEKGIY QTS NFRVQP TESIVRFPNV TNLCPFHEVF NATTFASVYA WNRTRISNCV ADYSVLYNFA PFFAFKCYGV SPTKLNDLCF TNVY ADSFV IKGNEVSQIA PGQTGNIADY NYKLPDDFTG CVIAWNSNKL DSKHSGNYDY WYRSLRKSKL KPFERDISTE IYQAG NKPC KGKGPNCYFP LQSYGFRPTY GVGHQPYRVV VLSFELLHAP ATVCGPKKST NLVKNKCVNF NFNGLTGTGV LTKSNK KFL PFQQFGRDIV DTTDAVRDPQ TLEILDITPC SFGGVSVITP GTNTSNQVAV LYQGVNCTEV SVAIHADQLT PTWRVYS TG SNVFQTRAGC LIGAEYVNNS YECDIPIGAG VCASYQTQTK SRGSASSVAS QSIIAYTMSL GAENSVAYSN NSIAIPTN F TISVTTEILP VSMTKTSVDC TMYICGDSTE CSNLLLQYGS FCTQLKRALT GIAVEQDKNT QEVFAQVKQI YKTPPIKYF GGFNFSQILP DPSKPSKRSP IEDLLFNKVT LADAGFIKQY GDCLGDIAAR DLICAQKFNG LTVLPPLLTD EMIAQYTSAL LAGTITSGW TFGAGPALQI PFPMQMAYRF NGIGVTQNVL YENQKLIANQ FNSAIGKIQD SLFSTPSALG KLQDVVNHNA Q ALNTLVKQ LSSKFGAISS VLNDILSRLD PPEAEVQIDR LITGRLQSLQ TYVTQQLIRA AEIRASANLA ATKMSECVLG QS KRVDFCG KGYHLMSFPQ SAPHGVVFLH VTYVPAQEKN FTTAPAICHD GKAHFPREGV FVSNGTHWFL TQRNFYEPQI ITT DNTFVS GNCDVVIGIV NNTVYDPLQL ELDSFKEELD KYFKNHTSPD VDLGDISGIN ASVVNIQKEI DRLNEVAKNL NESL IDLQE LGKYEQGSGY IPEAPRDGQA YVRKDGEWVF LSTFLSGLEV LFQGPGGWSH PQFEKGGGSG GGSGGSAWSH PQFEK GGSG LNDIFEAQKI EWHEHHHHHH HH |
-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 |
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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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About Yorodumi



Keywords
Homo sapiens (human)
Authors
China, 1 items
Citation






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Processing
FIELD EMISSION GUN
