+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36301 | |||||||||
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Title | Cryo-EM structure of the TcsH-TMPRSS2 complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | TcsH / TMPESS2 / TOXIN/HYDROLASE / TOXIN-HYDROLASE complex | |||||||||
Function / homology | Function and homology information transmembrane protease serine 2 / host cell cytosol / glycosyltransferase activity / protein autoprocessing / cysteine-type peptidase activity / Attachment and Entry / serine-type peptidase activity / host cell endosome membrane / toxin activity / viral translation ...transmembrane protease serine 2 / host cell cytosol / glycosyltransferase activity / protein autoprocessing / cysteine-type peptidase activity / Attachment and Entry / serine-type peptidase activity / host cell endosome membrane / toxin activity / viral translation / Induction of Cell-Cell Fusion / Attachment and Entry / positive regulation of viral entry into host cell / serine-type endopeptidase activity / lipid binding / host cell plasma membrane / proteolysis / extracellular exosome / extracellular region / nucleoplasm / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Paeniclostridium sordellii (bacteria) | |||||||||
Method | single particle reconstruction / Resolution: 3.2 Å | |||||||||
Authors | Zhou R / Tao L / Zhan X | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: Molecular basis of TMPRSS2 recognition by Paeniclostridium sordellii hemorrhagic toxin. Authors: Ruoyu Zhou / Liuqing He / Jiahao Zhang / Xiaofeng Zhang / Yanyan Li / Xiechao Zhan / Liang Tao / Abstract: Hemorrhagic toxin (TcsH) is a major virulence factor produced by Paeniclostridium sordellii, which is a non-negligible threat to women undergoing childbirth or abortions. Recently, Transmembrane ...Hemorrhagic toxin (TcsH) is a major virulence factor produced by Paeniclostridium sordellii, which is a non-negligible threat to women undergoing childbirth or abortions. Recently, Transmembrane Serine Protease 2 (TMPRSS2) was identified as a host receptor of TcsH. Here, we show the cryo-EM structures of the TcsH-TMPRSS2 complex and uncover that TcsH binds to the serine protease domain (SPD) of TMPRSS2 through the CROP unit-VI. This receptor binding mode is unique among LCTs. Five top surface loops of TMPRSS2, which also determine the protease substrate specificity, constitute the structural determinants recognized by TcsH. The binding of TcsH inhibits the proteolytic activity of TMPRSS2, whereas its implication in disease manifestations remains unclear. We further show that mutations selectively disrupting TMPRSS2-binding reduce TcsH toxicity in the intestinal epithelium of the female mice. These findings together shed light on the distinct molecular basis of TcsH-TMPRSS2 interactions, which expands our knowledge of host recognition mechanisms employed by LCTs and provides novel targets for developing therapeutics against P. sordellii infections. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36301.map.gz | 778.7 MB | EMDB map data format | |
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Header (meta data) | emd-36301-v30.xml emd-36301.xml | 17 KB 17 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36301_fsc.xml | 21 KB | Display | FSC data file |
Images | emd_36301.png | 37 KB | ||
Filedesc metadata | emd-36301.cif.gz | 6.8 KB | ||
Others | emd_36301_half_map_1.map.gz emd_36301_half_map_2.map.gz | 763.7 MB 763.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36301 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36301 | HTTPS FTP |
-Validation report
Summary document | emd_36301_validation.pdf.gz | 854.4 KB | Display | EMDB validaton report |
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Full document | emd_36301_full_validation.pdf.gz | 854 KB | Display | |
Data in XML | emd_36301_validation.xml.gz | 29.2 KB | Display | |
Data in CIF | emd_36301_validation.cif.gz | 38.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36301 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36301 | HTTPS FTP |
-Related structure data
Related structure data | 8jhzMC 8ji0C 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_36301.map.gz / Format: CCP4 / Size: 824 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: 1.087 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_36301_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36301_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : The TcsH-TMPRSS2 complex
Entire | Name: The TcsH-TMPRSS2 complex |
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Components |
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-Supramolecule #1: The TcsH-TMPRSS2 complex
Supramolecule | Name: The TcsH-TMPRSS2 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Hemorrhagic toxin
Macromolecule | Name: Hemorrhagic toxin / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Paeniclostridium sordellii (bacteria) |
Molecular weight | Theoretical: 300.675219 KDa |
Recombinant expression | Organism: Bacillus subtilis (bacteria) |
Sequence | String: MSLISKDELI KLAYSIKPRE DEYKTILTNL DEYNKLVTIN NKDKYLQLKK LNDSIDIFIN KYKKSSRNRA LFNLKKDISK EVILIKNSN ISPVEKNLHF VWIGGEVSDT ALEYINQWAD INRDYNIRVW YDGEAFLVNT LKKAIVEHST TDTLQLFEED I KNPQFDNM ...String: MSLISKDELI KLAYSIKPRE DEYKTILTNL DEYNKLVTIN NKDKYLQLKK LNDSIDIFIN KYKKSSRNRA LFNLKKDISK EVILIKNSN ISPVEKNLHF VWIGGEVSDT ALEYINQWAD INRDYNIRVW YDGEAFLVNT LKKAIVEHST TDTLQLFEED I KNPQFDNM KFYKKRMEFI YERQNRFINY YKSEINKPIK PTIDDIIKSH LVSEYNKNSE SLELYRRTSF EKISNNNGVD IR NNNLFTE QELLNIYNQE LLDRENLAAA SDLVRLLALK DFGGVYLDVD MLPGIQPDLF KTISRPSSIG VDSWEMIKLE AIM KYKKYI KNYTSKNFDK LDQQLKDDFQ ITLESKSEKS EIFSKLGNLD VSDLEIKIAF ALGSVINQAL ISKKGSYLTN LVIE QVKNR YKFLNQHLNP AIELGGNFSD TTKNFHDSLF NSATSENSMF LTKIASYLQV GFMPEARATI SLSGPGAYSS AYYDF INLQ DNTIEKTLNA SDLMEFKFPE SNLSQFTEQE IN(SEP)LWSFDQA SAKYQFEKYV RDYTQESLSE DSELDFNKNT VL DKNYLLN NKIPSNNVEE TGSKNYVHYI IQLQGDDISY ESACNLFSKN PKNSVIIQRN MNESAKSYFL SDNGESISEL NKY RIPQRL KNKEKIKVTF IGHGKDEFNT SEFAKLSVDS LSNEISSFLD IMKLDISPKN VEINLLGCNM FSYNVNVEET YPGK LLLNN IDKIISTLPN VNKDNITIGA NQYEVRINNE GRKELLDHSG QWLNKEEAIM NDLSSKEYIF FDSIENRPKA KSKNL IELA SISDNIKTLL LDTNIDPETK FILNNLKLNI ESSIDNNIYY EKLEPVKNII HNSIDNLTNE FNLIENVSDE LYELKK INN LDDNYLISFE DISKNDSTYT IRFINKNSGE SVHIQTEKEI FLKYGEHITQ EINTIKNNII IDVNGNLIGN IELEHAP QV NTLNAAFFIQ SLIDYSNNKD VLNNLRTSVK VQLYAQLFST GLNTIYDSIQ LVNLISNAIN DAINVLPTLT EGVPILAT I LDGISLGAAI KELSETNDPL LKKELEAKVG IIAINMSLSL ASMISTVIGV GSELAIFLLP IAGISAGIPS LVNNELILH DKATSVVNYF THLSESKKYG PFKLEDDKIL SPIDDLVISE IDFNTDSIKL GTCDILSMEG GSGYTVTNDI DHFFSSPYIN SNIPPLSIY PVMNIQTTNL DFSKDLMMLP NAPSRLLWWE TGAVPGLRSL ETDGTRLLDS IRDFYPGKFY WRFYAWFDFA I TTLKPVYE NTNIKIKLDK NTRNFIMPTI TTDVIRNNLS YSFTGSGGTY SLLLSSHPIS TNINLSKDDL WIFNIDNKVR EI SIQNGTI KKGNLVRNAL SNLDINKNKL TIDNQIINFS GDVDNKYRYI FLNCSLDDEI SLMIEINLFA KSYNLILSGN KDY LISNLS TIINKINNLG LNSKNISYNY TDEFNNKYFG VISKTNQKSI ICYKKGSKNI LELYNGNMLL FDSKDFIADD INIF MKDDI NTITGKYYID NNLDISVDFS ISLISKNKVK VNGLYLNEYG YASFLEFIKN SDGHHNTSNF INLFLDNIGF WKLFG FNNI EFVIDKYFAI TGKTDMGYIE FICDNNKNID IYFGEWKTSS TKNTIFSGNG RNLIVEPIYD INAGDNISTS IDFSYE YIS GIDIYINKIL IVPNLYTELV NINTDYSSNK YFPEIIVLNT DTFHDKVNIN LDSSSLDYEW AIDGSDFILS RYLEENN RK ILQKIRIKDI LSNTKSFNKM MIDFKDIKNI SLDHIMNNFK SFNSESELDR DHFGFKTIDS KTYYYNEVGK LVKGSINI N DSLFYFDTIE SNLVTGWKTI NGKTYYFDIN NGVAYIGYKT IDGKNFYFDG NGIMQIGVFK VPDGFKYFAP ANTYNNNEE GQTIVYQNKF LTINGKKYYF DNNSKAVTGW QIINGNKYYF DTNTGIAAVG LQIINNNKYY FNPHTAIAAT GWQSINNAKY YFDINTYIG TTGYKTIDSK NFYFDSNCIM QIGVFKVSDG FKYFAPANTY NNNEEGQAIV YQNKFLTING KRYYFDNNSK A VTGWHTID GKKYYFNPNT AIAATGWHTI DDKKYYFNPD TAIAATGWHT IDDKKYYFNP NTGITSTGET TINNKSFYFN DK GIMQIGV FKVPDGFKYF APANTHNNNL EGQAIVYQNK FLTINGKKYY FDNNSKAITG WQVIDDKKYY FNSNTAVADT NLC TINNEK YYFSYDGILQ NGYITIGRLN FYFDSNNDSK MTTGVFKGPN GFEYFAPANT YNNNLEGQAI VYQNKFLTIN GKKY YFDNK SKAVTGWQTI DGKKYYFNPN TAIAAMGWQA IDGKKYYFNP NTAIATTGWQ TIDGKKYYFN PNTAIAATGW QAIDG KKYY FNPNTATTSI GYTTINSKNF YFNNDGIMQL GVFKGPDGFE YFAPANTHNN NEEGQSITYQ NKFLIFNEDV YYFDSS SKA VTGWRTIDDH RFYFEPNTGI GANGYKTLDG KNFYFRNGLP QFGVFKGPDG FEYFAPANTH NNNEEGQSIT YQNKFLV FL GNRYYFDSSS KAVTGWQTIN GNTYYFMPDT AIAAAGGFFT IDGAIYFFGI DGVKQPGIYG HHHHHHHH UniProtKB: Hemorrhagic toxin |
-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: 46.712984 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GHHHHHHWKF MGSKCSNSGI ECDSSGTCIN PSNWCDGVSH CPGGEDENRC VRLYGPNFI LQVYSSQRKS WHPVCQDDWN ENYGRAACRD MGYKNNFYSS QGIVDDSGST SFMKLNTSAG NVDIYKKLYH S DACSSKAV ...String: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GHHHHHHWKF MGSKCSNSGI ECDSSGTCIN PSNWCDGVSH CPGGEDENRC VRLYGPNFI LQVYSSQRKS WHPVCQDDWN ENYGRAACRD MGYKNNFYSS QGIVDDSGST SFMKLNTSAG NVDIYKKLYH S DACSSKAV VSLRCIACGV NLNSSRQSQI VGGESALPGA WPWQVSLHVQ NVHVCGGSII TPEWIVTAAH CVEKPLNNPW HW TAFAGIL RQSFMFYGAG YQVEKVISHP NYDSKTKNND IALMKLQKPL TFNDLVKPVC LPNPGMMLQP EQLCWISGWG ATE EKGKTS EVLNAAKVLL IETQRCNSRY VYDNLITPAM ICAGFLQGNV DSCQGDSGGP LVTSKNNIWW LIGDTSWGSG CAKA YRPGV YGNVMVFTDW IYRQMRADG UniProtKB: Transmembrane protease serine 2 |
-Macromolecule #3: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 3 / Number of copies: 1 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Processing | single particle reconstruction |
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Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k 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: 2.0 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |