Protein: Cytotoxin-L (EC 3.4.22.-) (Lethal toxin) (LT) [Cleaved into: Glucosyltransferase TcsL (EC 2.4.1.-)] (Q46342)
Organism: Paraclostridium sordellii (Clostridium sordellii)
Function: Precursor of a cytotoxin that targets the vascular endothelium, inducing an anti-inflammatory effect and resulting in lethal toxic shock syndrome. TcsL constitutes the main toxin that mediates the pathology of P.sordellii infection, an anaerobic Gram-positive bacterium found in soil and in the gastrointestinal and vaginal tracts of animals and humans; although the majority of carriers are asymptomatic, pathogenic P.sordellii infections arise rapidly and are highly lethal. This form constitutes the precursor of the toxin: it enters into host cells and mediates autoprocessing to release the active toxin (Glucosyltransferase TcsL) into the host cytosol. Targets vascular endothelium by binding to the semaphorin proteins SEMA6A and SEMA6B, and enters host cells via clathrin-mediated endocytosis. Once entered into host cells, acidification in the endosome promotes the membrane insertion of the translocation region and formation of a pore, leading to translocation of the GT44 and peptidase C80 domains across the endosomal membrane (By similarity). This activates the peptidase C80 domain and autocatalytic processing, releasing the N-terminal part (Glucosyltransferase TcsL), which constitutes the active part of the toxin, in the cytosol.
Subcellular location: [Cytotoxin-L]: Secreted {ECO:0000250|UniProtKB:P18177}. Host endosome membrane {ECO:0000250|UniProtKB:P18177}. Note=Secreted from P.sordellii cell into the extracellular environment via help of holin-like protein TcdE/UtxA (By similarity). Binds to the cell surface receptors via the receptor-binding region and enters the cells via clathrin-mediated endocytosis (By similarity). Acidification in the endosome triggers conformational changes that promote the membrane insertion of the translocation region, allowing formation of a pore, leading to translocation of the GT44 and peptidase C80 domains across the endosomal membrane (By similarity). 1D-myo-inositol hexakisphosphate-binding (InsP6) activates the peptidase C80 domain and autoprocessing, generating the Glucosyltransferase TcsL form, which is released in the host cytosol (PubMed:17334356). {ECO:0000250|UniProtKB:P18177, ECO:0000269|PubMed:17334356}.; SUBCELLULAR LOCATION: [Glucosyltransferase TcsL]: Host cytoplasm, host cytosol {ECO:0000305|PubMed:8626586}. Host cell membrane {ECO:0000269|PubMed:27023605, ECO:0000269|PubMed:27303685}; Peripheral membrane protein {ECO:0000269|PubMed:27023605}; Cytoplasmic side {ECO:0000269|PubMed:27023605}. Note=Binding to phospholipids, such as phosphatidylserine and phosphatidic acid promotes localization to the inner face of the cell membrane close to its membrane anchored substrates (small GTPases). {ECO:0000269|PubMed:25882477, ECO:0000269|PubMed:27023605}.
Interaction partners:
Sequence:
MNLVNKAQLQKMVYVKFRIQEDEYVAILNALEEYHNMSESSVVEKYLKLKDINNLTDNYLNTYKKSGRNKALKKFKEYLTMEVLELKNNSLTPVEKNLHFIWIGGQINDTAINYINQWKDVNSDYTVKVFYDSNAFLINTLKKTIVESATNNTLESFRENLNDPEFDYNKFYRKRMEIIYDKQKHFIDYYKSQIEENPEFIIDNIIKTYLSNEYSKDLEALNKYIEESLNKITANNGNDIRNLEKFADEDLVRLYNQELVERWNLAAASDILRISMLKEDGGVYLDVDILPGIQPDLFKSINKPDSITNTSWEMIKLEAIMKYKEYIPGYTSKNFDMLDEEVQRSFESALSSKSDKSEIFLPLDDIKVSPLEVKIAFANNSVINQALISLKDSYCSDLVINQIKNRYKILNDNLNPSINEGTDFNTTMKIFSDKLASISNEDNMMFMIKITNYLKVGFAPDVRSTINLSGPGVYTGAYQDLLMFKDNSTNIHLLEPELRNFEFPKTKISQLTEQEITSLWSFNQARAKSQFEEYKKGYFEGALGEDDNLDFAQNTVLDKDYVSKKILSSMKTRNKEYIHYIVQLQGDKISYEASCNLFSKDPYSSILYQKNIEGSETAYYYYVADAEIKEIDKYRIPYQISNKRNIKLTFIGHGKSEFNTDTFANLDVDSLSSEIETILNLAKADISPKYIEINLLGCNMFSYSISAEETYPGKLLLKIKDRVSELMPSISQDSITVSANQYEVRINEEGKREILDHSGKWINKEESIIKDISSKEYISFNPKENKIIVKSKYLHELSTLLQEIRNNANSSDIDLEKKVMLTECEINVASNIDRQIVEGRIEEAKNLTSDSINYIKNEFKLIESISDSLYDLKHQNGLDDSHFISFEDISKTENGFRIRFINKETGNSIFIETEKEIFSEYATHISKEISNIKDTIFDNVNGKLVKKVNLDAAHEVNTLNSAFFIQSLIEYNTTKESLSNLSVAMKVQVYAQLFSTGLNTITDASKVVELVSTALDETIDLLPTLSEGLPIIATIIDGVSLGAAIKELSETNDPLLRQEIEAKIGIMAVNLTAASTAIVTSALGIASGFSILLVPLAGISAGIPSLVNNELILQDKATKVIDYFKHISLAETEGAFTLLDDKIIMPQDDLVLSEIDFNNNSITLGKCEIWRAEGGSGHTLTDDIDHFFSSPSITYRKPWLSIYDVLNIKKEKIDFSKDLMVLPNAPNRVFGYEMGWTPGFRSLDNDGTKLLDRIRDHYEGQFYWRYFAFIADALITKLKPRYEDTNVRINLDGNTRSFIVPVITTEQIRKNLSYSFYGSGGSYSLSLSPYNMNIDLNLVENDTWVIDVDNVVKNITIESDEIQKGELIENILSKLNIEDNKIILNNHTINFYGDINESNRFISLTFSILEDINIIIEIDLVSKSYKILLSGNCMKLIENSSDIQQKIDHIGFNGEHQKYIPYSYIDNETKYNGFIDYSKKEGLFTAEFSNESIIRNIYMPDSNNLFIYSSKDLKDIRIINKGDVKLLIGNYFKDDMKVSLSFTIEDTNTIKLNGVYLDENGVAQILKFMNNAKSALNTSNSLMNFLESINIKNIFYNNLDPNIEFILDTNFIISGSNSIGQFELICDKDKNIQPYFINFKIKETSYTLYVGNRQNLIVEPSYHLDDSGNISSTVINFSQKYLYGIDRYVNKVIIAPNLYTDEINITPVYKPNYICPEVIILDANYINEKINVNINDLSIRYVWDNDGSDLILIANSEEDNQPQVKIRFVNVFKSDTAADKLSFNFSDKQDVSVSKIISTFSLAAYSDGFFDYEFGLVSLDNDYFYINSFGNMVSGLIYINDSLYYFKPPKNNLITGFTTIDGNKYYFDPTKSGAASIGEITIDGKDYYFNKQGILQVGVINTSDGLKYFAPAGTLDENLEGESVNFIGKLNIDGKIYYFEDNYRAAVEWKLLDDETYYFNPKTGEALKGLHQIGDNKYYFDDNGIMQTGFITINDKVFYFNNDGVMQVGYIEVNGKYFYFGKNGERQLGVFNTPDGFKFFGPKDDDLGTEEGELTLYNGILNFNGKIYFFDISNTAVVGWGTLDDGSTYYFDDNRAEACIGLTVINDCKYYFDDNGIRQLGFITINDNIFYFSESGKIELGYQNINGNYFYIDESGLVLIGVFDTPDGYKYFAPLNTVNDNIYGQAVKYSGLVRVNEDVYYFGETYKIETGWIENETDKYYFDPETKKAYKGINVVDDIKYYFDENGIMRTGLISFENNNYYFNEDGKMQFGYLNIKDKMFYFGKDGKMQIGVFNTPDGFKYFAHQNTLDENFEGESINYTGWLDLDGKRYYFTDEYIAATGSLTIDGYNYYFDPDTAELVVSE