SSL3_STAA8
ID SSL3_STAA8 Reviewed; 356 AA.
AC Q2G0X7;
DT 03-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 25-MAY-2022, entry version 87.
DE RecName: Full=Staphylococcal superantigen-like 3 {ECO:0000303|PubMed:22665377};
DE Flags: Precursor;
GN Name=ssl3 {ECO:0000303|PubMed:22665377}; OrderedLocusNames=SAOUHSC_00386;
OS Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=93061;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NCTC 8325 / PS 47;
RA Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.;
RT "The Staphylococcus aureus NCTC 8325 genome.";
RL (In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.);
RL Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington
RL D.C. (2006).
RN [2]
RP FUNCTION, AND INTERACTION WITH HOST TLR2.
RX PubMed=22665377; DOI=10.1128/iai.00399-12;
RA Yokoyama R., Itoh S., Kamoshida G., Takii T., Fujii S., Tsuji T.,
RA Onozaki K.;
RT "Staphylococcal superantigen-like protein 3 binds to the Toll-like receptor
RT 2 extracellular domain and inhibits cytokine production induced by
RT Staphylococcus aureus, cell wall component, or lipopeptides in murine
RT macrophages.";
RL Infect. Immun. 80:2816-2825(2012).
RN [3]
RP FUNCTION, INTERACTION WITH HOST TLR2, AND MUTAGENESIS OF ARG-338.
RC STRAIN=NCTC 8325 / PS 47;
RX PubMed=22714643; DOI=10.1007/s00109-012-0926-8;
RA Bardoel B.W., Vos R., Bouman T., Aerts P.C., Bestebroer J., Huizinga E.G.,
RA Brondijk T.H., van Strijp J.A., de Haas C.J.;
RT "Evasion of Toll-like receptor 2 activation by staphylococcal superantigen-
RT like protein 3.";
RL J. Mol. Med. 90:1109-1120(2012).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=NCTC 8325 / PS 47;
RX PubMed=28858870; DOI=10.1159/000479100;
RA Koymans K.J., Goldmann O., Karlsson C.A.Q., Sital W., Thaenert R.,
RA Bisschop A., Vrieling M., Malmstroem J., van Kessel K.P.M., de Haas C.J.C.,
RA van Strijp J.A.G., Medina E.;
RT "The TLR2 Antagonist Staphylococcal Superantigen-Like Protein 3 Acts as a
RT Virulence Factor to Promote Bacterial Pathogenicity in vivo.";
RL J. Innate Immun. 9:561-573(2017).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 164-356, MUTAGENESIS OF PHE-186
RP AND PHE-188, FUNCTION, INTERACTION WITH HOST TLR2, AND DOMAIN.
RX PubMed=26283364; DOI=10.1073/pnas.1502026112;
RA Koymans K.J., Feitsma L.J., Brondijk T.H., Aerts P.C., Lukkien E.,
RA Loessl P., van Kessel K.P., de Haas C.J., van Strijp J.A., Huizinga E.G.;
RT "Structural basis for inhibition of TLR2 by staphylococcal superantigen-
RT like protein 3 (SSL3).";
RL Proc. Natl. Acad. Sci. U.S.A. 112:11018-11023(2015).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 31-356, AND DOMAIN.
RG Center for Structural Genomics of Infectious Diseases (CSGID);
RA Minasov G., Nocadello S., Shuvalova L., Filippova E.V., Halavaty A.,
RA Dubrovska I., Bagnoli F., Falugi F., Bottomley M., Grandi G.,
RA Anderson W.F.;
RT "1.75 Angstrom Crystal Structure of Superantigen-like Protein, Exotoxin
RT from Staphylococcus aureus, in Complex with Sialyl-LewisX.";
RL Submitted (FEB-2016) to the PDB data bank.
CC -!- FUNCTION: Secreted protein that plays an essential role in immune
CC innate response inhibition by interacting with and inhibiting host
CC TLR2. In turn, bacteria recognition by immune cells is impaired and
CC cytokine production is inhibited (PubMed:22665377, PubMed:22714643).
CC Mechanistically, by interacting with TLR2, blocks ligand binding and
CC thus inhibits activation (PubMed:26283364). Second, by interacting with
CC an already formed TLR2-lipopeptide complex, prevents TLR
CC heterodimerization and downstream signaling. The interaction with host
CC TLR2 does not involve sialyl Lewis X interactions (PubMed:26283364).
CC {ECO:0000269|PubMed:22665377, ECO:0000269|PubMed:22714643,
CC ECO:0000269|PubMed:26283364}.
CC -!- SUBUNIT: Interacts with host TLR2 (via its extracellular domain).
CC {ECO:0000269|PubMed:22665377, ECO:0000269|PubMed:22714643,
CC ECO:0000269|PubMed:26283364}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28858870}.
CC -!- DOMAIN: The C-terminal domain contains a V-shape binding site for
CC sialyl Lewis X. {ECO:0000269|PubMed:26283364}.
CC -!- SIMILARITY: Belongs to the staphylococcal/streptococcal toxin family.
CC {ECO:0000305}.
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DR EMBL; CP000253; ABD29550.1; -; Genomic_DNA.
DR RefSeq; WP_000784023.1; NZ_LS483365.1.
DR RefSeq; YP_498973.1; NC_007795.1.
DR PDB; 5D3D; X-ray; 1.94 A; A/B=164-356.
DR PDB; 5D3I; X-ray; 3.20 A; B=164-356.
DR PDB; 5I4D; X-ray; 1.75 A; A/B=31-356.
DR PDBsum; 5D3D; -.
DR PDBsum; 5D3I; -.
DR PDBsum; 5I4D; -.
DR AlphaFoldDB; Q2G0X7; -.
DR SMR; Q2G0X7; -.
DR STRING; 1280.SAXN108_0478; -.
DR UniLectin; Q2G0X7; -.
DR EnsemblBacteria; ABD29550; ABD29550; SAOUHSC_00386.
DR GeneID; 3919122; -.
DR KEGG; sao:SAOUHSC_00386; -.
DR PATRIC; fig|93061.5.peg.355; -.
DR HOGENOM; CLU_054950_1_0_9; -.
DR OMA; FMNVIPD; -.
DR Proteomes; UP000008816; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR InterPro; IPR008992; Enterotoxin.
DR InterPro; IPR015282; SSL_OB.
DR InterPro; IPR006126; Staph/Strept_toxin_CS.
DR InterPro; IPR008375; Staph_exotoxin.
DR InterPro; IPR016091; SuperAg_toxin_C.
DR InterPro; IPR013307; Superantigen_bac.
DR Pfam; PF09199; SSL_OB; 1.
DR PRINTS; PR01898; SAGSUPRFAMLY.
DR PRINTS; PR01800; STAPHEXOTOXN.
DR SUPFAM; SSF50203; SSF50203; 1.
DR SUPFAM; SSF54334; SSF54334; 1.
DR PROSITE; PS00278; STAPH_STREP_TOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Reference proteome; Secreted; Signal; Virulence.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..356
FT /note="Staphylococcal superantigen-like 3"
FT /evidence="ECO:0000255"
FT /id="PRO_0000447509"
FT REGION 61..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 228..326
FT /note="Sialyl Lewis X-binding"
FT /evidence="ECO:0000269|PubMed:26283364"
FT COMPBIAS 71..100
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 101..163
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 186
FT /note="F->A: About 100-fold reduction in cytokine
FT production, when associated with A-188."
FT /evidence="ECO:0000269|PubMed:26283364"
FT MUTAGEN 188
FT /note="F->A: About 100-fold reduction in cytokine
FT production, when associated with A-188."
FT /evidence="ECO:0000269|PubMed:26283364"
FT MUTAGEN 338
FT /note="R->A: About 75% loss of human TLR2 binding."
FT /evidence="ECO:0000269|PubMed:22714643"
FT HELIX 169..174
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 180..189
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 193..196
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 198..201
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 203..206
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:5I4D"
FT HELIX 216..219
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 225..232
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 242..247
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 259..268
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 274..283
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:5I4D"
FT HELIX 290..305
FT /evidence="ECO:0007829|PDB:5I4D"
FT TURN 307..309
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 314..320
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:5I4D"
FT HELIX 336..340
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:5I4D"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:5I4D"
FT STRAND 348..355
FT /evidence="ECO:0007829|PDB:5I4D"
SQ SEQUENCE 356 AA; 40181 MW; 32C655251E8E87A5 CRC64;
MKMRTIAKTS LALGLLTTGA ITVTTQSVKA EKIQSTKVDK VPTLKAERLA MINITAGANS
ATTQAANTRQ ERTPKLEKAP NTNEEKTSAS KIEKISQPKQ EEQKTLNISA TPAPKQEQSQ
TTTESTTPKT KVTTPPSTNT PQPMQSTKSD TPQSPTIKQA QTDMTPKYED LRAYYTKPSF
EFEKQFGFML KPWTTVRFMN VIPNRFIYKI ALVGKDEKKY KDGPYDNIDV FIVLEDNKYQ
LKKYSVGGIT KTNSKKVNHK VELSITKKDN QGMISRDVSE YMITKEEISL KELDFKLRKQ
LIEKHNLYGN MGSGTIVIKM KNGGKYTFEL HKKLQEHRMA DVIDGTNIDN IEVNIK
