TACY_CLOPE
ID TACY_CLOPE Reviewed; 500 AA.
AC P0C2E9; P19995;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 25-MAY-2022, entry version 96.
DE RecName: Full=Perfringolysin O;
DE Short=PFO;
DE AltName: Full=Theta-toxin;
DE AltName: Full=Thiol-activated cytolysin;
DE Flags: Precursor;
GN Name=pfo; Synonyms=pfoA, pfoR; OrderedLocusNames=CPE0163;
OS Clostridium perfringens (strain 13 / Type A).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=195102;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1987025; DOI=10.1128/iai.59.1.137-142.1991;
RA Shimizu T., Okabe A., Minami J., Hayashi H.;
RT "An upstream regulatory sequence stimulates expression of the
RT perfringolysin O gene of Clostridium perfringens.";
RL Infect. Immun. 59:137-142(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=13 / Type A;
RX PubMed=11792842; DOI=10.1073/pnas.022493799;
RA Shimizu T., Ohtani K., Hirakawa H., Ohshima K., Yamashita A., Shiba T.,
RA Ogasawara N., Hattori M., Kuhara S., Hayashi H.;
RT "Complete genome sequence of Clostridium perfringens, an anaerobic flesh-
RT eater.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:996-1001(2002).
RN [3]
RP PROTEIN SEQUENCE OF 29-45 AND 305-312, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 10543 / DSM 798 / NCIB 8875 / BP6K / Type A;
RX PubMed=2878682; DOI=10.1021/bi00368a032;
RA Ohno-Iwashita Y., Iwamoto M., Mitsui K., Kawasaki H., Ando S.;
RT "Cold-labile hemolysin produced by limited proteolysis of theta-toxin from
RT Clostridium perfringens.";
RL Biochemistry 25:6048-6053(1986).
RN [4]
RP IMPORTANCE OF THIOL-GROUP IN CHOLESTEROL BINDING.
RX PubMed=2888650; DOI=10.1111/j.1432-1033.1987.tb13355.x;
RA Iwamoto M., Ohno-Iwashita Y., Ando S.;
RT "Role of the essential thiol group in the thiol-activated cytolysin from
RT Clostridium perfringens.";
RL Eur. J. Biochem. 167:425-430(1987).
RN [5]
RP FUNCTION, CHOLESTEROL-BINDING, AND MUTAGENESIS OF 490-THR-LEU-491; THR-490
RP AND LEU-491.
RX PubMed=20145114; DOI=10.1073/pnas.0911581107;
RA Farrand A.J., LaChapelle S., Hotze E.M., Johnson A.E., Tweten R.K.;
RT "Only two amino acids are essential for cytolytic toxin recognition of
RT cholesterol at the membrane surface.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:4341-4346(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=8955365; DOI=10.1016/s0014-5793(96)01200-8;
RA Feil S.C., Rossjohn J., Rohde K., Tweten R.K., Parker M.W.;
RT "Crystallization and preliminary X-ray analysis of a thiol-activated
RT cytolysin.";
RL FEBS Lett. 397:290-292(1996).
RN [7] {ECO:0007744|PDB:1PFO}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND DOMAIN.
RX PubMed=9182756; DOI=10.1016/s0092-8674(00)80251-2;
RA Rossjohn J., Feil S.C., McKinstry W.J., Tweten R.K., Parker M.W.;
RT "Structure of a cholesterol-binding, thiol-activated cytolysin and a model
RT of its membrane form.";
RL Cell 89:685-692(1997).
RN [8] {ECO:0007744|PDB:2BK1, ECO:0007744|PDB:2BK2}
RP STRUCTURE BY ELECTRON MICROSCOPY (28.00 ANGSTROMS) OF 36-500 (PREPORE),
RP STRUCTURE BY ELECTRON MICROSCOPY (29.00 ANGSTROMS) OF 36-500 (PORE),
RP SUBUNIT, AND DOMAIN.
RX PubMed=15851031; DOI=10.1016/j.cell.2005.02.033;
RA Tilley S.J., Orlova E.V., Gilbert R.J., Andrew P.W., Saibil H.R.;
RT "Structural basis of pore formation by the bacterial toxin pneumolysin.";
RL Cell 121:247-256(2005).
RN [9] {ECO:0007744|PDB:1M3I, ECO:0007744|PDB:1PFO}
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 30-500, AND FUNCTION.
RX PubMed=17328912; DOI=10.1016/j.jmb.2007.01.042;
RA Rossjohn J., Polekhina G., Feil S.C., Morton C.J., Tweten R.K.,
RA Parker M.W.;
RT "Structures of perfringolysin O suggest a pathway for activation of
RT cholesterol-dependent cytolysins.";
RL J. Mol. Biol. 367:1227-1236(2007).
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 assembles into a pre-pore complex. A
CC major conformational change leads to insertion in the host membrane and
CC formation of an oligomeric pore complex. Cholesterol is required for
CC binding to host cell membranes, membrane insertion and pore formation;
CC cholesterol binding is mediated by a Thr-Leu pair in the C-terminus.
CC Can be reversibly inactivated by oxidation.
CC {ECO:0000269|PubMed:17328912, ECO:0000269|PubMed:20145114}.
CC -!- SUBUNIT: Modeling based on cryo-EM shows a homooligomeric pore complex
CC containing 38-44 subunits; when inserted in the host membrane.
CC {ECO:0000269|PubMed:15851031}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2878682}. Host cell
CC membrane; Multi-pass membrane protein {ECO:0000305|PubMed:15851031}.
CC Note=Secreted as soluble protein that then inserts into the host cell
CC membrane and forms huge pores formed by transmembrane beta-strands.
CC {ECO:0000305|PubMed:15851031}.
CC -!- DOMAIN: Mature protein has 3 discontinuous domains; D1, D2, D3 followed
CC by C-terminal D4; the domains rearrange substantially upon membrane
CC insertion (PubMed:9182756, PubMed:15851031). A highly conserved
CC undecapeptide in the D4 domain has residues important for membrane
CC binding and cell lysis, and penetrates into the upper leaflet of
CC cholesterol-rich bilayers in the pre-pore complex (PubMed:15851031).
CC {ECO:0000269|PubMed:15851031, ECO:0000269|PubMed:9182756}.
CC -!- SIMILARITY: Belongs to the cholesterol-dependent cytolysin family.
CC {ECO:0000305}.
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DR EMBL; M81080; AAA23271.1; -; Genomic_DNA.
DR EMBL; BA000016; BAB79869.1; -; Genomic_DNA.
DR PIR; B43577; B43577.
DR RefSeq; WP_003467630.1; NC_003366.1.
DR PDB; 1M3I; X-ray; 2.90 A; A/B/C/D=30-500.
DR PDB; 1M3J; X-ray; 3.00 A; A/B=30-500.
DR PDB; 1PFO; X-ray; 2.20 A; A=1-500.
DR PDB; 2BK1; EM; 29.00 A; A=53-500.
DR PDB; 2BK2; EM; 28.00 A; A=36-500.
DR PDB; 5DHL; X-ray; 2.67 A; A/B=29-500.
DR PDB; 5DIM; X-ray; 3.32 A; A=29-500.
DR PDBsum; 1M3I; -.
DR PDBsum; 1M3J; -.
DR PDBsum; 1PFO; -.
DR PDBsum; 2BK1; -.
DR PDBsum; 2BK2; -.
DR PDBsum; 5DHL; -.
DR PDBsum; 5DIM; -.
DR AlphaFoldDB; P0C2E9; -.
DR SMR; P0C2E9; -.
DR STRING; 195102.gene:10489407; -.
DR TCDB; 1.C.12.1.1; the thiol-activated cholesterol-dependent cytolysin (cdc) family.
DR ABCD; P0C2E9; 3 sequenced antibodies.
DR EnsemblBacteria; BAB79869; BAB79869; BAB79869.
DR KEGG; cpe:CPE0163; -.
DR HOGENOM; CLU_026912_1_0_9; -.
DR OMA; NDRTYPG; -.
DR EvolutionaryTrace; P0C2E9; -.
DR Proteomes; UP000000818; 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; IMP:CACAO.
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 3D-structure; Cytolysis; Direct protein sequencing; Hemolysis;
KW Host cell membrane; Host membrane; Lipid-binding; Membrane;
KW Reference proteome; Secreted; Signal; Toxin; Transmembrane;
KW Transmembrane beta strand; Virulence.
FT SIGNAL 1..28
FT /evidence="ECO:0000269|PubMed:2878682"
FT CHAIN 29..500
FT /note="Perfringolysin O"
FT /id="PRO_0000034104"
FT TRANSMEM 189..202
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT TRANSMEM 209..218
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT TRANSMEM 287..296
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT TRANSMEM 304..316
FT /note="Beta stranded"
FT /evidence="ECO:0000250|UniProtKB:Q04IN8"
FT MOTIF 458..468
FT /note="Conserved undecapeptide"
FT /evidence="ECO:0000305"
FT MOTIF 490..491
FT /note="Cholesterol binding"
FT /evidence="ECO:0000269|PubMed:20145114"
FT SITE 459
FT /note="Important for cholesterol binding"
FT /evidence="ECO:0000305|PubMed:2888650"
FT MUTAGEN 490..491
FT /note="TL->AA,GG,LT: Loss of hemolytic activity, loss of
FT host membrane binding, loss of cholesterol binding."
FT /evidence="ECO:0000269|PubMed:20145114"
FT MUTAGEN 490
FT /note="T->A,G,S: Loss of hemolytic activity."
FT /evidence="ECO:0000269|PubMed:20145114"
FT MUTAGEN 491
FT /note="L->A,G,I,V: Severely impaired hemolytic activity."
FT /evidence="ECO:0000269|PubMed:20145114"
FT CONFLICT 30
FT /note="D -> K (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 34
FT /note="K -> I (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 71
FT /note="T -> A (in Ref. 1; AAA23271)"
FT /evidence="ECO:0000305"
FT HELIX 38..43
FT /evidence="ECO:0007829|PDB:1PFO"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 52..56
FT /evidence="ECO:0007829|PDB:5DHL"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 72..87
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:1PFO"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 129..133
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:5DHL"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 151..168
FT /evidence="ECO:0007829|PDB:1PFO"
FT TURN 169..171
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 178..185
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 189..196
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 200..206
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 211..215
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 218..235
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 241..244
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 251..256
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 260..263
FT /evidence="ECO:0007829|PDB:5DHL"
FT STRAND 265..284
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 290..299
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 302..305
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 307..314
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 316..324
FT /evidence="ECO:0007829|PDB:1PFO"
FT TURN 328..331
FT /evidence="ECO:0007829|PDB:1M3I"
FT STRAND 333..336
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 338..347
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 359..366
FT /evidence="ECO:0007829|PDB:1PFO"
FT TURN 367..369
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 377..390
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 392..398
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:1M3I"
FT STRAND 404..415
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 421..427
FT /evidence="ECO:0007829|PDB:1PFO"
FT TURN 429..432
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 437..445
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 449..458
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:1PFO"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 469..475
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 480..488
FT /evidence="ECO:0007829|PDB:1PFO"
FT STRAND 490..499
FT /evidence="ECO:0007829|PDB:1PFO"
SQ SEQUENCE 500 AA; 55830 MW; E5584B7347413EF2 CRC64;
MIRFKKTKLI ASIAMALCLF SQPVISFSKD ITDKNQSIDS GISSLSYNRN EVLASNGDKI
ESFVPKEGKK TGNKFIVVER QKRSLTTSPV DISIIDSVND RTYPGALQLA DKAFVENRPT
ILMVKRKPIN INIDLPGLKG ENSIKVDDPT YGKVSGAIDE LVSKWNEKYS STHTLPARTQ
YSESMVYSKS QISSALNVNA KVLENSLGVD FNAVANNEKK VMILAYKQIF YTVSADLPKN
PSDLFDDSVT FNDLKQKGVS NEAPPLMVSN VAYGRTIYVK LETTSSSKDV QAAFKALIKN
TDIKNSQQYK DIYENSSFTA VVLGGDAQEH NKVVTKDFDE IRKVIKDNAT FSTKNPAYPI
SYTSVFLKDN SVAAVHNKTD YIETTSTEYS KGKINLDHSG AYVAQFEVAW DEVSYDKEGN
EVLTHKTWDG NYQDKTAHYS TVIPLEANAR NIRIKARECT GLAWEWWRDV ISEYDVPLTN
NINVSIWGTT LYPGSSITYN
