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Yorodumi- EMDB-39026: Local structure of HCoV-HKU1A spike in complex with TMPRSS2 and glycan -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-39026 | |||||||||
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Title | Local structure of HCoV-HKU1A spike in complex with TMPRSS2 and glycan | |||||||||
Map data | ||||||||||
Sample |
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Keywords | HKU1A / spike / TMPRSS2 / VIRAL PROTEIN | |||||||||
Function / homology | Function and homology information transmembrane protease serine 2 / protein autoprocessing / Attachment and Entry / serine-type peptidase activity / endocytosis involved in viral entry into host cell / viral translation / Induction of Cell-Cell Fusion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / positive regulation of viral entry into host cell ...transmembrane protease serine 2 / protein autoprocessing / Attachment and Entry / serine-type peptidase activity / endocytosis involved in viral entry into host cell / viral translation / Induction of Cell-Cell Fusion / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / fusion of virus membrane with host plasma membrane / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / viral envelope / host cell plasma membrane / virion membrane / proteolysis / extracellular exosome / extracellular region / nucleoplasm / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Human coronavirus HKU1 / Human coronavirus HKU1 (isolate N1) / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.24 Å | |||||||||
Authors | Wang HF / Zhang X / Lu Y / Liu X / Sun L / Yang HT | |||||||||
Funding support | China, 1 items
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Citation | Journal: Cell / Year: 2024 Title: TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry. Authors: Haofeng Wang / Xiaoce Liu / Xiang Zhang / Zhuoqian Zhao / Yuchi Lu / Dingzhe Pu / Zeyang Zhang / Jie Chen / Yajie Wang / Mengfei Li / Xuxue Dong / Yinkai Duan / Yujia He / Qiyu Mao / ...Authors: Haofeng Wang / Xiaoce Liu / Xiang Zhang / Zhuoqian Zhao / Yuchi Lu / Dingzhe Pu / Zeyang Zhang / Jie Chen / Yajie Wang / Mengfei Li / Xuxue Dong / Yinkai Duan / Yujia He / Qiyu Mao / Hangtian Guo / Haoran Sun / Yihan Zhou / Qi Yang / Yan Gao / Xiuna Yang / Hongzhi Cao / Luke Guddat / Lei Sun / Zihe Rao / Haitao Yang / Abstract: The entry of coronaviruses is initiated by spike recognition of host cellular receptors, involving proteinaceous and/or glycan receptors. Recently, TMPRSS2 was identified as the proteinaceous ...The entry of coronaviruses is initiated by spike recognition of host cellular receptors, involving proteinaceous and/or glycan receptors. Recently, TMPRSS2 was identified as the proteinaceous receptor for HCoV-HKU1 alongside sialoglycan as a glycan receptor. However, the underlying mechanisms for viral entry remain unknown. Here, we investigated the HCoV-HKU1C spike in the inactive, glycan-activated, and functionally anchored states, revealing that sialoglycan binding induces a conformational change of the NTD and promotes the neighboring RBD of the spike to open for TMPRSS2 recognition, exhibiting a synergistic mechanism for the entry of HCoV-HKU1. The RBD of HCoV-HKU1 features an insertion subdomain that recognizes TMPRSS2 through three previously undiscovered interfaces. Furthermore, structural investigation of HCoV-HKU1A in combination with mutagenesis and binding assays confirms a conserved receptor recognition pattern adopted by HCoV-HKU1. These studies advance our understanding of the complex viral-host interactions during entry, laying the groundwork for developing new therapeutics against coronavirus-associated diseases. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_39026.map.gz | 161 MB | EMDB map data format | |
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Header (meta data) | emd-39026-v30.xml emd-39026.xml | 17.2 KB 17.2 KB | Display Display | EMDB header |
Images | emd_39026.png | 61.5 KB | ||
Filedesc metadata | emd-39026.cif.gz | 6.8 KB | ||
Others | emd_39026_half_map_1.map.gz emd_39026_half_map_2.map.gz | 226.3 MB 226.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-39026 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-39026 | HTTPS FTP |
-Validation report
Summary document | emd_39026_validation.pdf.gz | 817.8 KB | Display | EMDB validaton report |
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Full document | emd_39026_full_validation.pdf.gz | 817.4 KB | Display | |
Data in XML | emd_39026_validation.xml.gz | 16.1 KB | Display | |
Data in CIF | emd_39026_validation.cif.gz | 19 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-39026 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-39026 | HTTPS FTP |
-Related structure data
Related structure data | 8y7yMC 8y7xC 8y87C 8y88C 8y89C 8y8aC 8y8bC 8y8cC 8y8dC 8y8eC 8y8fC 8y8gC 8y8hC 8y8iC 8y8jC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_39026.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: 0.82 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_39026_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_39026_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : HKU1A-TMPRSS2 complex
Entire | Name: HKU1A-TMPRSS2 complex |
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Components |
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-Supramolecule #1: HKU1A-TMPRSS2 complex
Supramolecule | Name: HKU1A-TMPRSS2 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Human coronavirus HKU1 |
-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Human coronavirus HKU1 (isolate N1) |
Molecular weight | Theoretical: 141.235328 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: VIGDFNCTNF AINDLNTTVP RISEYVVDVS YGLGTYYILD RVYLNTTILF TGYFPKSGAN FRDLSLKGTT YLSTLWYQKP FLSDFNNGI FSRVKNTKLY VNKTLYSEFS TIVIGSVFIN NSYTIVVQPH NGVLEITACQ YTMCEYPHTI CKSKGSSRNE S WHFDKSEP ...String: VIGDFNCTNF AINDLNTTVP RISEYVVDVS YGLGTYYILD RVYLNTTILF TGYFPKSGAN FRDLSLKGTT YLSTLWYQKP FLSDFNNGI FSRVKNTKLY VNKTLYSEFS TIVIGSVFIN NSYTIVVQPH NGVLEITACQ YTMCEYPHTI CKSKGSSRNE S WHFDKSEP LCLFKKNFTY NVSTDWLYFH FYQERGTFYA YYADSGMPTT FLFSLYLGTL LSHYYVLPLT CNAISSNTDN ET LQYWVTP LSKRQYLLKF DNRGVITNAV DCSSSFFSEI QCKTKSLLPN TGVYDLSGFT VKPVATVHRR IPDLPDCDID KWL NNFNVP SPLNWERKIF SNCNFNLSTL LRLVHTDSFS CNNFDESKIY GSCFKSIVLD KFAIPNSRRS DLQLGSSGFL QSSN YKIDT TSSSCQLYYS LPAINVTINN YNPSSWNRRY GFNNFNLSSH SVVYSRYCFS VNNTFCPCAK PSFASSCKSH KPPSA SCPI GTNYRSCEST TVLDHTDWCR CSCLPDPITA YDPRSCSQKK SLVGVGEHCA GFGVDEEKCG VLDGSYNVSC LCSTDA FLG WSYDTCVSNN RCNIFSNFIL NGINSGTTCS NDLLQPNTEV FTDVCVDYDL YGITGQGIFK EVSAVYYNSW QNLLYDS NG NIIGFKDFVT NKTYNIFPCY AGRVSAAFHQ NASSLALLYR NLKCSYVLNN ISLTTQPYFD SYLGCVFNAD NLTDYSVS S CALRMGSGFC VDYNSPSSSS SGGSGSSISA SYRFVTFEPF NVSFVNDSIE SVGGLYEIKI PTNFTIVGQE EFIQTNSPK VTIDCSLFVC SNYAACHDLL SEYGTFCDNI NSILDEVNGL LDTTQLHVAD TLMQGVTLSS NLNTNLHFDV DNINFKSLVG CLGPHCGSS SRSFFEDLLF DKVKLSDVGF VEAYNNCTGG SEIRDLLCVQ SFNGIKVLPP ILSESQISGY TTAATVAAMF P PWSAAAGI PFSLNVQYRI NGLGVTMDVL NKNQKLIATA FNNALLSIQN GFSATNSALA KIQSVVNSNA QALNSLLQQL FN KFGAISS SLQEILSRLD PPEAQVQIDR LINGRLTALN AYVSQQLSDI SLVKFGAALA MEKVNECVKS QSPRINFCGN GNH ILSLVQ NAPYGLLFMH FSYKPISFKT VLVSPGLCIS GDVGIAPKQG YFIKHNDHWM FTGSSYYYPE PISDKNVVFM NTCS VNFTK APLVYLNHSV PKLSDFESEL SHWFKNQTSI APNLTLNLHT INATFLDLYY EMNLIQESIK SLN UniProtKB: Spike glycoprotein |
-Macromolecule #2: Transmembrane protease serine 2
Macromolecule | Name: Transmembrane protease serine 2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: transmembrane protease serine 2 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 42.283629 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGSKCSNSGI ECDSSGTCIN PSNWCDGVSH CPGGEDENRC VRLYGPNFIL QVYSSQRKSW HPVCQDDWNE NYGRAACRDM GYKNNFYSS QGIVDDSGST SFMKLNTSAG NVDIYKKLYH SDACSSKAVV SLRCIACGVN LNDDDDKIVG GESALPGAWP W QVSLHVQN ...String: MGSKCSNSGI ECDSSGTCIN PSNWCDGVSH CPGGEDENRC VRLYGPNFIL QVYSSQRKSW HPVCQDDWNE NYGRAACRDM GYKNNFYSS QGIVDDSGST SFMKLNTSAG NVDIYKKLYH SDACSSKAVV SLRCIACGVN LNDDDDKIVG GESALPGAWP W QVSLHVQN VHVCGGSIIT PEWIVTAAHC VEKPLNNPWH WTAFAGILRQ SFMFYGAGYQ VEKVISHPNY DSKTKNNDIA LM KLQKPLT FNDLVKPVCL PNPGMMLQPE QLCWISGWGA TEEKGKTSEV LNAAKVLLIE TQRCNSRYVY DNLITPAMIC AGF LQGNVD SCQGDSGGPL VTSKNNIWWL IGDTSWGSGC AKAYRPGVYG NVMVFTDWIY RQMRADG UniProtKB: Transmembrane protease serine 2 |
-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: 4 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #7: methyl 9-O-acetyl-5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galac...
Macromolecule | Name: methyl 9-O-acetyl-5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosidonic acid type: ligand / ID: 7 / Number of copies: 1 / Formula: MJJ |
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Molecular weight | Theoretical: 365.333 Da |
Chemical component information | ChemComp-MJJ: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / 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: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.24 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 315373 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |