ID   TACY_STRP3              Reviewed;         571 AA.
AC   P0DF96; P0A4L0; P21131;
DT   27-JUL-2011, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 1.
DT   25-MAY-2022, entry version 55.
DE   RecName: Full=Streptolysin O;
DE            Short=SLO;
DE   AltName: Full=Thiol-activated cytolysin;
DE   Flags: Precursor;
GN   Name=slo; OrderedLocusNames=SpyM3_0130;
OS   Streptococcus pyogenes serotype M3 (strain ATCC BAA-595 / MGAS315).
OC   Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC   Streptococcus.
OX   NCBI_TaxID=198466;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Richards / Serotype M3;
RX   PubMed=3502717; DOI=10.1128/iai.55.12.3228-3232.1987;
RA   Kehoe M.A., Miller L., Walker J.A., Boulnois G.J.;
RT   "Nucleotide sequence of the streptolysin O (SLO) gene: structural
RT   homologies between SLO and other membrane-damaging, thiol-activated
RT   toxins.";
RL   Infect. Immun. 55:3228-3232(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-595 / MGAS315;
RX   PubMed=12122206; DOI=10.1073/pnas.152298499;
RA   Beres S.B., Sylva G.L., Barbian K.D., Lei B., Hoff J.S., Mammarella N.D.,
RA   Liu M.-Y., Smoot J.C., Porcella S.F., Parkins L.D., Campbell D.S.,
RA   Smith T.M., McCormick J.K., Leung D.Y.M., Schlievert P.M., Musser J.M.;
RT   "Genome sequence of a serotype M3 strain of group A Streptococcus: phage-
RT   encoded toxins, the high-virulence phenotype, and clone emergence.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:10078-10083(2002).
RN   [3]
RP   MUTAGENESIS OF CYS-530.
RX   PubMed=2663727; DOI=10.1128/iai.57.8.2553-2558.1989;
RA   Pinkney M., Beachey E., Kehoe M.;
RT   "The thiol-activated toxin streptolysin O does not require a thiol group
RT   for cytolytic activity.";
RL   Infect. Immun. 57:2553-2558(1989).
CC   -!- FUNCTION: A cholesterol-dependent toxin that causes cytolysis by
CC       forming pores in cholesterol containing host membranes. After binding
CC       to target membranes, the protein undergoes a major conformation change,
CC       leading to its insertion in the host membrane and formation of an
CC       oligomeric pore complex. Cholesterol is required for binding to host
CC       membranes, membrane insertion and pore formation; cholesterol binding
CC       is mediated by a Thr-Leu pair in the C-terminus. Can be reversibly
CC       inactivated by oxidation. {ECO:0000250|UniProtKB:P13128}.
CC   -!- SUBUNIT: Homooligomeric pore complex of 35 to 50 subunits; when
CC       inserted in the host membrane. {ECO:0000250|UniProtKB:Q04IN8}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P0C2J9}. Host
CC       cell membrane {ECO:0000250|UniProtKB:P13128}; Multi-pass membrane
CC       protein {ECO:0000250|UniProtKB:Q04IN8}. Note=Probably secreted as
CC       soluble protein by the accessory Sec system (By similarity). It then
CC       inserts into the host cell membrane and forms pores formed by
CC       transmembrane beta-strands (By similarity).
CC       {ECO:0000250|UniProtKB:P0C2J9, ECO:0000250|UniProtKB:Q04IN8}.
CC   -!- SIMILARITY: Belongs to the cholesterol-dependent cytolysin family.
CC       {ECO:0000305}.
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DR   EMBL; M18638; AAA26975.1; -; Genomic_DNA.
DR   EMBL; AE014074; AAM78737.1; -; Genomic_DNA.
DR   PIR; A43507; A43507.
DR   RefSeq; WP_010921831.1; NC_004070.1.
DR   AlphaFoldDB; P0DF96; -.
DR   SMR; P0DF96; -.
DR   EnsemblBacteria; AAM78737; AAM78737; SpyM3_0130.
DR   GeneID; 57851997; -.
DR   KEGG; spg:SpyM3_0130; -.
DR   HOGENOM; CLU_026912_1_0_9; -.
DR   OMA; NDRTYPG; -.
DR   Proteomes; UP000000564; Chromosome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0015485; F:cholesterol binding; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.40.1430; -; 1.
DR   Gene3D; 3.90.840.10; -; 1.
DR   InterPro; IPR035390; Thiol_cytolys_C.
DR   InterPro; IPR038700; Thiol_cytolys_C_sf.
DR   InterPro; IPR001869; Thiol_cytolysin.
DR   InterPro; IPR036363; Thiol_cytolysin_ab_sf.
DR   InterPro; IPR036359; Thiol_cytolysin_sf.
DR   Pfam; PF17440; Thiol_cytolys_C; 1.
DR   Pfam; PF01289; Thiol_cytolysin; 1.
DR   PRINTS; PR01400; TACYTOLYSIN.
DR   SUPFAM; SSF56978; SSF56978; 1.
DR   PROSITE; PS00481; THIOL_CYTOLYSINS; 1.
PE   1: Evidence at protein level;
KW   Cytolysis; Hemolysis; Host cell membrane; Host membrane; Lipid-binding;
KW   Membrane; Secreted; Signal; Toxin; Transmembrane;
KW   Transmembrane beta strand; Virulence.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000255"
FT   CHAIN           34..571
FT                   /note="Streptolysin O"
FT                   /id="PRO_0000034108"
FT   TRANSMEM        260..273
FT                   /note="Beta stranded"
FT                   /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT   TRANSMEM        280..289
FT                   /note="Beta stranded"
FT                   /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT   TRANSMEM        358..367
FT                   /note="Beta stranded"
FT                   /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT   TRANSMEM        375..387
FT                   /note="Beta stranded"
FT                   /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT   REGION          30..108
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           529..539
FT                   /note="Conserved undecapeptide"
FT                   /evidence="ECO:0000305"
FT   MOTIF           561..562
FT                   /note="Cholesterol binding"
FT                   /evidence="ECO:0000250|UniProtKB:P0C2E9"
FT   COMPBIAS        30..53
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        83..108
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         530
FT                   /note="C->A,S: No loss of hemolytic activity."
FT                   /evidence="ECO:0000269|PubMed:2663727"
SQ   SEQUENCE   571 AA;  63638 MW;  D05AA9979DCBCAB0 CRC64;
     MSNKKTFKKY SRVAGLLTAA LIIGNLVTAN AESNKQNTAS TETTTTNEQP KPESSELTTE
     KAGQKTDDML NSNDMIKLAP KEMPLESAEK EEKKSEDKKK SEEDHTEEIN DKIYSLNYNE
     LEVLAKNGET IENFVPKEGV KKADKFIVIE RKKKNINTTP VDISIIDSVT DRTYPAALQL
     ANKGFTENKP DAVVTKRNPQ KIHIDLPGMG DKATVEVNDP TYANVSTAID NLVNQWHDNY
     SGGNTLPART QYTESMVYSK SQIEAALNVN SKILDGTLGI DFKSISKGEK KVMIAAYKQI
     FYTVSANLPN NPADVFDKSV TFKELQRKGV SNEAPPLFVS NVAYGRTVFV KLETSSKSND
     VEAAFSAALK GTDVKTNGKY SDILENSSFT AVVLGGDAAE HNKVVTKDFD VIRNVIKDNA
     TFSRKNPAYP ISYTSVFLKN NKIAGVNNRT EYVETTSTEY TSGKINLSHQ GAYVAQYEIL
     WDEINYDDKG KEVITKRRWD NNWYSKTSPF STVIPLGANS RNIRIMAREC TGLAWEWWRK
     VIDERDVKLS KEINVNISGS TLSPYGSITY K