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PR01501

Identifier
TOXICSSTOXIN  [View Relations]  [View Alignment]  
Accession
PR01501
No. of Motifs
9
Creation Date
28-MAR-2001
Title
Staphylococcal toxic shock syndrome toxin signature
Database References

PROSITE; PS00278 STAPH_STREP_TOXIN_2
BLOCKS; BL00277
PFAM; PF01123 Stap_Strp_toxin
INTERPRO; IPB001961
PDB; 3TSS; 2QIL; 1TS5
SCOP; 3TSS; 2QIL; 1TS5
CATH; 3TSS; 2QIL; 1TS5
Literature References
1. BLOMSTER-HAUTAMAA, D.A., KREISWIRTH, B.N., KORNBLUM, J.S., NOVICK, R.P.
AND SCHLIEVERT, P.M.
The nucleotide and partial amino acid sequence of toxic shock syndrome 
toxin-1.
J.BIOL.CHEM. 261 15783-15786 (1986).
 
2. ACHARYA, K.R., PASSALACQUA, E.F., JONES, E.Y., HARLOS, K., STUART, D.I., 
BREHM, R.D. AND TRANTER, H.S. 
Structural basis of superantigen action inferred from crystal structure of 
toxic-shock syndrome toxin-1.
NATURE 367 94-97 (1994). 
 
3. PRASAD, G.S., EARHART, C.A., MURRAY, D.L., NOVICK, R.P., SCHLIEVERT, P.M.
AND OHLENDORF, D.H.
Structure of toxic shock syndrome toxin 1.
BIOCHEMISTRY 32 13761-13766 (1993). 
 
4. PRASAD, G.S, RADHAKRISHAN, R., MITCHELL, D.T., EARHART, C.A.,
DINGES, M.M., COOK, W.J., SCHLIEVERT, P.M. AND OHLENDORF, D.H.
Refined structures of three crystal forms of toxic shock syndrome toxin-1
and of a tetramutant with reduced activity.
PROTEIN SCI. 6 1220-1227 (1997).

Documentation
DINGES, M.M., COOK, W.J., SCHLIEVERT, P.M. AND OHLENDORF, D.H.
Staphylococcus aureus is a Gram-positive coccus that grows in clusters or
pairs, and is the major cause of nosocomial infections due to its multiple 
antibiotic resistant nature [1]. Patients who are immunocompromised (e.g., 
those suffering from third degree burns or chronic illness) are at risk 
from deep staphylococcal infections, such as osteomyelitis and pneumonia.
Most skin infections are also caused by this bacterium [1].
 
Many virulence mechanisms are employed by Staphylococci to induce 
pathogenesis: these can include polysaccharide capsules and exotoxins [1].
One of the major virulence exotoxins is toxic shock syndrome toxin (TSST),
which is secreted by the organism upon successful invasion. It causes a
major inflammatory response in the host via superantigenic properties [2],
and is the causative agent of toxic shock syndrome.
 
The structure of the TSST protein was originally determined to 2.5A by means
of X-ray crystallography [2]. The N- and C-terminal domains both contain
regions involved in MHC class II association; the C-terminal domain is also
implicated in binding the T-cell receptor [2]. Overall, the structure 
resembles that of Staphylococcal enterotoxin B (SEB) [3], but differs in its
N-terminus and in the degree to which a long central helix is covered by 
surface loops [3]. The region around the carboxyl end of this helix is 
proposed to govern the superantigenic properties of TSST [3]. An adjacent
region along this helix is thought to be critical in the ability of TSST
to induce toxic shock syndrome [3]. Most recently, the structures of five 
mutants of TSST have been determined to 1.95A [4]. The mutations are in 
the central alpha-helix, and allow mapping of portions of TSST involved in
superantigenicity and lethality [4].
 
TOXICSSTOXIN is a 9-element fingerprint that provides a signature for 
Staphylococcal toxic shock syndrome toxin-1. The fingerprint was derived
from an initial alignment of 3 sequences: the motifs were drawn from
conserved regions spanning the full alignment length (~220 amino acids) - 
motif 2 encodes alpha-helix 1 of the 1.9A resolved structure; motif 3 spans
beta-strands 1 and 2; motif 4 encodes strands 4 and 5; motif 5 spans strands
6-8; motif 6 spans the N-terminus of strand 9 and strands 10 and 11; motif 7
encodes the bulk of helix 2 and the N-terminal residues of strand 13; motif
8 spans the C-terminus of strand 13 and strand 14; and motif 9 spans strand
15 and helix 4. A single iteration on SPTR37_10f was required to reach 
convergence, no further sequences being identified beyond the starting set.
Four partial matches were found (Q9ZFS4, Q9ZFS6, Q9ZFS5 and Q9RN32) all of
which are Staphyloccocal exotoxins that match motifs 2, 7, 8 and/or 9.
Summary Information
   3 codes involving  9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
4 codes involving 2 elements
Composite Feature Index
9333333333
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2020000411
123456789
True Positives
O54462        Q9ZFS3        TSST_STAAU    
True Positive Partials
Codes involving 2 elements
Q9RN32 Q9ZFS4 Q9ZFS5 Q9ZFS6
Sequence Titles
O54462      TOXIC SHOCK SYNDROME TOXIN-1 - Staphylococcus aureus. 
Q9ZFS3 Exotoxin 4 - Staphylococcus aureus.
TSST_STAAU TOXIC SHOCK SYNDROME TOXIN-1 PRECURSOR (TSST-1) - Staphylococcus aureus.

Q9RN32 Exotoxin 1 - Staphylococcus aureus.
Q9ZFS4 Exotoxin 5 - Staphylococcus aureus.
Q9ZFS5 Exotoxin 1 - Staphylococcus aureus.
Q9ZFS6 Exotoxin 3 - Staphylococcus aureus.
Scan History
SPTR39_15f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
LLLATIATDFTPVPLSSNQ O54462 15 15 -
LLLATTATDFTPVPLSSNQ TSST_STAAU 15 15 -
LTTGTLTTEAHSGHAKQNQ Q9ZFS3 16 16 -

Motif 2 width=18
Element Seqn Id St Int Rpt
KASTNDNIKDLLDWYSSG O54462 39 5 -
KASTNDNIKDLLDWYSSG TSST_STAAU 39 5 -
KSVNKHDKEALHRYYTGN Q9ZFS3 35 0 -

Motif 3 width=15
Element Seqn Id St Int Rpt
NSEVLDNSLGSMRIK O54462 62 5 -
NSEVLDNSLGSMRIK TSST_STAAU 62 5 -
NINALRHGKNNLRFK Q9ZFS3 58 5 -

Motif 4 width=24
Element Seqn Id St Int Rpt
YYSPAFTKGEKVDLNTKRTKKSQH O54462 91 14 -
YYSPAFTKGEKVDLNTKRTKKSQH TSST_STAAU 91 14 -
YRKYQQRRHTGLDVFFVQERRDKH Q9ZFS3 87 14 -

Motif 5 width=21
Element Seqn Id St Int Rpt
IHFQISGVTNTEKLPTPIELP O54462 121 6 -
IHFQISGVTNTEKLPTPIELP TSST_STAAU 121 6 -
ISYTVGGVTKTNKTSGFVSTP Q9ZFS3 112 1 -

Motif 6 width=18
Element Seqn Id St Int Rpt
KVHGKDSPLKYWPKFDKK O54462 145 3 -
KVHGKDSPLKYGPKFDKK TSST_STAAU 145 3 -
KEKGEDAFVKGYPYDIKK Q9ZFS3 138 5 -

Motif 7 width=23
Element Seqn Id St Int Rpt
LDFEIRHQLTQIHGLYRSSDKTG O54462 169 6 -
LDFEIRHQLTQIHGLYRSSDKTG TSST_STAAU 169 6 -
LDFKLRKHLIEKYGLYKTLSKDG Q9ZFS3 163 7 -

Motif 8 width=17
Element Seqn Id St Int Rpt
KITMNDGSTYQSDLSKK O54462 195 3 -
KITMNDGSTYQSDLSKK TSST_STAAU 195 3 -
KISLKDGSFYNLDLRTK Q9ZFS3 188 2 -

Motif 9 width=14
Element Seqn Id St Int Rpt
INIDEIKTIEAEIN O54462 221 9 -
INIDEIKTIEAEIN TSST_STAAU 221 9 -
IDSKQIKDIEVNLK Q9ZFS3 214 9 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
LLLATIATDFTPVPLSSNQ O54462 15 15 -
LLLATTATDFTPVPLSSNQ TSST_STAAU 15 15 -
LTTGTLTTEAHSGHAKQNQ Q9ZFS3 16 16 -

Motif 2 width=18
Element Seqn Id St Int Rpt
KASTNDNIKDLLDWYSSG O54462 39 5 -
KASTNDNIKDLLDWYSSG TSST_STAAU 39 5 -
KSVNKHDKEALHRYYTGN Q9ZFS3 35 0 -

Motif 3 width=15
Element Seqn Id St Int Rpt
NSEVLDNSLGSMRIK O54462 62 5 -
NSEVLDNSLGSMRIK TSST_STAAU 62 5 -
NINALRHGKNNLRFK Q9ZFS3 58 5 -

Motif 4 width=24
Element Seqn Id St Int Rpt
YYSPAFTKGEKVDLNTKRTKKSQH O54462 91 14 -
YYSPAFTKGEKVDLNTKRTKKSQH TSST_STAAU 91 14 -
YRKYQQRRHTGLDVFFVQERRDKH Q9ZFS3 87 14 -

Motif 5 width=21
Element Seqn Id St Int Rpt
IHFQISGVTNTEKLPTPIELP O54462 121 6 -
IHFQISGVTNTEKLPTPIELP TSST_STAAU 121 6 -
ISYTVGGVTKTNKTSGFVSTP Q9ZFS3 112 1 -

Motif 6 width=18
Element Seqn Id St Int Rpt
KVHGKDSPLKYWPKFDKK O54462 145 3 -
KVHGKDSPLKYGPKFDKK TSST_STAAU 145 3 -
KEKGEDAFVKGYPYDIKK Q9ZFS3 138 5 -

Motif 7 width=23
Element Seqn Id St Int Rpt
LDFEIRHQLTQIHGLYRSSDKTG O54462 169 6 -
LDFEIRHQLTQIHGLYRSSDKTG TSST_STAAU 169 6 -
LDFKLRKHLIEKYGLYKTLSKDG Q9ZFS3 163 7 -

Motif 8 width=17
Element Seqn Id St Int Rpt
KITMNDGSTYQSDLSKK O54462 195 3 -
KITMNDGSTYQSDLSKK TSST_STAAU 195 3 -
KISLKDGSFYNLDLRTK Q9ZFS3 188 2 -

Motif 9 width=14
Element Seqn Id St Int Rpt
INIDEIKTIEAEIN O54462 221 9 -
INIDEIKTIEAEIN TSST_STAAU 221 9 -
IDSKQIKDIEVNLK Q9ZFS3 214 9 -