SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01774

Identifier
EXFOLTOXIN  [View Relations]  [View Alignment]  
Accession
PR01774
No. of Motifs
6
Creation Date
18-NOV-2002  (UPDATE 03-APR-2003)
Title
Exfoliative toxin signature
Database References

PDB; 1EXF
SCOP; 1EXF
CATH; 1EXF
Literature References
1. DINGES, M.M., ORWIN, P.M. AND SCHLIEVERT, P.M.
Exotoxins of Staphylococcus aureus. 
CLIN.MICROBIOL.REV. 13 16-34 (2000).
 
2. LLEWELYN, M. AND COHEN, J.
Superantigens: microbial agents that corrupt immunity.
LANCET INFECT.DIS. 2 156-162 (2002).
 
3. MCCORMICK, J.K., YARWOOD, Y.M. AND SCHLIEVERT, P.M.
Toxic shock syndrome and bacterial superantigens: an update.
ANNU.REV.MICROBIOL. 55 77-104 (2001). 
 
4. LADHANI, S., JOANNOU, C.L., LOCHRIE, D.P., EVANS, R.W. AND POSTON, S.M.
Clinical, microbial, and biochemical aspects of the exfoliative toxins
causing staphylococcal scalded-skin syndrome.
CLIN.MICROBIOL.REV. 12 224-242 (1999).
 
5. CAVARELLI, J., PREVOST, G., BOURGUET, W., MOULINIER, L., CHEVRIER, B., 
DELAGOUTTE, B., BILWES, A., MOUREY, L., RIFAI, S., PIEMONT, Y. AND MORAS, D.
The structure of Staphylococcus aureus epidermolytic toxin A, an atypic
serine protease, at 1.7 A resolution.
STRUCTURE 5 813-824 (1997).

Documentation
The prokaryote Staphylococcus aureus is a well-characterised and specialised
human pathogen, expressing a variety of virulence factors to enable
successful infection of the host [1]. Symptoms usually manifest in cases of 
food poisoning, pyrogenic fever and toxic shock syndrome, and can prove 
lethal in immunocompromised victims [1]. Of all the exotoxins secreted from 
the bacterial cell, superantigens and hemolysins are amongst the most 
studied [1]. 
 
Of these, the former are well characterised, and several S.aureus super-
antigenic enterotoxins exist that trigger excessive and aberrant T-cell
activation in the host. Homologues of these S.aureus proteins have been 
found in Streptococcus pyogenes, and cause similar effects [2]. In 
conventional Major Histocompatibility Complex (MHC)-II-restricted antigen 
processing, a peptide epitope is presented to a specific T-cell receptor 
(TCR) by the antigen presenting cell, and up to 0.0001% of the host T-cell 
repertoire is activated [2]. By contrast, a bacterial superantigen (SAg) can 
bypass this process, binding non-specifically to constant regions on both 
the MHC-II and TCR [2]. This results in up to 25% of the total host T-cell 
population being activated, with a massive release of inflammatory cytokines 
as a consequence. 
 
A recent study into the origins and functions of the S.aureus and S.pyogenes
superantigens has identified distinct protein domains that are responsible 
for the slightly different actions of each protein subgroup [3]. Based on 
these criteria, the staphylococcal and streptococcal entero-/exotoxins 
discovered so far can be placed into several groups/subfamilies [3]. The 
EXFOL group contains those superantigens that cause exfoliative skin 
diseases in the human host, and shows some similarity to staphylococcal
serine proteases [4]. Although these proteins show no significant sequence
similarity to the more "conventional" SAgs, they do function in the same way,
binding both TCR and MHC-II molecules [4]. 
 
The EXFOL group of exotoxins also possess potent serine protease activity, 
and contain a functional domain found in other S.aureus serine proteases 
[4]. To date, two distinct members of the subfamily have been characterised, 
both from S.aureus, and designated Exfoliative toxin A and B (Eta and Etb) 
[4]. The tertiary structure of Eta has been resolved to 1.7A using X-ray
crystallography [5]. This reveals that Eta contains unique "ETA-surface
loops", no cysteine bridges, and a specific N-terminal helix that is 
crucial for substrate hydrolysis [5]. 
 
EXFOLTOXIN is a 6-element fingerprint that provides a signature for the
exfoliative toxins. The fingerprint was derived from an initial alignment
of 3 sequences: the motifs were drawn from conserved regions spanning
virtually the full alignment length - motif 1 spans alpha-helix 4 and beta-
strands 2 and 3; motif 2 spans strands 4 and 5 and helices 5 and 6, and 
includes the active site histidine; motif 3 includes strand 8; motif 4 spans
strand 9 and helix 8, and includes the active site aspartic acid; motif 5 
spans helix 9 and strand 11; and motif 6 spans the C-terminus of strand 13,
helix 11, strand 14 and the N-terminus of strand 15, and contains the active
site serine. A single iteration on SPTR40_20f was required to reach
convergence, no further sequences being identified beyond the starting set.
Several partial matches were found, all serine proteases that match motifs
2, 4 and 6, which contain the catalytic triad residues. 
Summary Information
   3 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
3 codes involving 3 elements
5 codes involving 2 elements
Composite Feature Index
6333333
5000000
4000000
3030303
2040105
123456
True Positives
ETA_STAAU     ETB_STAAU     Q9KWH0        
True Positive Partials
Codes involving 3 elements
Q04186 Q99V45 STSP_STAAU
Codes involving 2 elements
Q8ZBM6 Q99T60 Q9FBG1 Q9FD08
Q9KH51
Sequence Titles
ETA_STAAU   Exfoliative toxin A precursor (EC 3.4.21.-) (Epidermolytic toxin A) - Staphylococcus aureus. 
ETB_STAAU Exfoliative toxin B precursor (EC 3.4.21.-) (Epidermolytic toxin B) - Staphylococcus aureus.
Q9KWH0 EXFOLIATIVE TOXIN B - Staphylococcus hyicus.

Q04186 GLUTAMIC ACID SPECIFIC PROTEASE PREPROPEPTIDE (EC 3.4.21.19) - Staphylococcus aureus.
Q99V45 SERINE PROTEASE, V8 PROTEASE, GLUTAMYL ENDOPEPTIDASE - Staphylococcus aureus (strain Mu50 / ATCC 700699), and Staphylococcus aureus (strain N315).
STSP_STAAU Glutamyl endopeptidase precursor (EC 3.4.21.19) (Staphylococcal serine proteinase) (V8 proteinase) (Endoproteinase GLU-C) - Staphylococcus aureus.

Q8ZBM6 GLOBAL STRESS REQUIREMENT PROTEIN GSRA - Yersinia pestis.
Q99T60 SERINE PROTEASE SPLA - Staphylococcus aureus (strain Mu50 / ATCC 700699), and Staphylococcus aureus (strain N315).
Q9FBG1 GLUTAMYL ENDOPEPTIDASE - Staphylococcus warneri.
Q9FD08 SERINE PROTEASE-LIKE EXOPROTEIN A - Staphylococcus aureus.
Q9KH51 SERINE PROTEASE SPLA - Staphylococcus aureus.
Scan History
SPTR40_20f 1  75   NSINGLE    
Initial Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
PYSAVGTVFVKDGLLATGVLIG Q9KWH0 57 57 -
PYNSVGTVFVKGSTLATGVLIG ETB_STAAU 66 66 -
PYNTIGNVFVKGQTSATGVLIG ETA_STAAU 80 80 -

Motif 2 width=25
Element Seqn Id St Int Rpt
KNTIITNTHVARLAKQDPSKVSFTP Q9KWH0 79 0 -
KNTIVTNYHVAREAAKNPSNIIFTP ETB_STAAU 88 0 -
KNTVLTNRHIAKFANGDPSKVSFRP ETA_STAAU 102 0 -

Motif 3 width=18
Element Seqn Id St Int Rpt
PYGQFAAEDINESPYGGG Q9KWH0 116 12 -
PYGKFEAEEIKESPYGQG ETB_STAAU 126 13 -
PYGEYEVKEILQEPFGAG ETA_STAAU 139 12 -

Motif 4 width=23
Element Seqn Id St Int Rpt
DLSIIKLKPNANGKSAGDLITPA Q9KWH0 135 1 -
DLAIIKLKPNEKGESAGDLIQPA ETB_STAAU 145 1 -
DLALIRLKPDQNGVSLGDKISPA ETA_STAAU 158 1 -

Motif 5 width=19
Element Seqn Id St Int Rpt
IPDSIDLQPGDKISLLGYP Q9KWH0 159 1 -
IPDHIDIQKGDKYSLLGYP ETB_STAAU 169 1 -
IGTSNDLKDGDKLELIGYP ETA_STAAU 182 1 -

Motif 6 width=25
Element Seqn Id St Int Rpt
YFGYTEPGNSGSGIFNLNGELVGIH Q9KWH0 200 22 -
YFGYTEVGNSGSGIFNLKGELIGIH ETB_STAAU 208 20 -
YYGFTVPGNSGSGIFNSNGELVGIH ETA_STAAU 224 23 -
Final Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
PYSAVGTVFVKDGLLATGVLIG Q9KWH0 57 57 -
PYNSVGTVFVKGSTLATGVLIG ETB_STAAU 66 66 -
PYNTIGNVFVKGQTSATGVLIG ETA_STAAU 80 80 -

Motif 2 width=25
Element Seqn Id St Int Rpt
KNTIITNTHVARLAKQDPSKVSFTP Q9KWH0 79 0 -
KNTIVTNYHVAREAAKNPSNIIFTP ETB_STAAU 88 0 -
KNTVLTNRHIAKFANGDPSKVSFRP ETA_STAAU 102 0 -

Motif 3 width=18
Element Seqn Id St Int Rpt
PYGQFAAEDINESPYGGG Q9KWH0 116 12 -
PYGKFEAEEIKESPYGQG ETB_STAAU 126 13 -
PYGEYEVKEILQEPFGAG ETA_STAAU 139 12 -

Motif 4 width=23
Element Seqn Id St Int Rpt
DLSIIKLKPNANGKSAGDLITPA Q9KWH0 135 1 -
DLAIIKLKPNEKGESAGDLIQPA ETB_STAAU 145 1 -
DLALIRLKPDQNGVSLGDKISPA ETA_STAAU 158 1 -

Motif 5 width=19
Element Seqn Id St Int Rpt
IPDSIDLQPGDKISLLGYP Q9KWH0 159 1 -
IPDHIDIQKGDKYSLLGYP ETB_STAAU 169 1 -
IGTSNDLKDGDKLELIGYP ETA_STAAU 182 1 -

Motif 6 width=25
Element Seqn Id St Int Rpt
YFGYTEPGNSGSGIFNLNGELVGIH Q9KWH0 200 22 -
YFGYTEVGNSGSGIFNLKGELIGIH ETB_STAAU 208 20 -
YYGFTVPGNSGSGIFNSNGELVGIH ETA_STAAU 224 23 -