The spectral and thermodynamic properties of staphylococcal enterotoxin A, E, and variants suggest that structural modifications are important to control their function.


Abstract

The superantigens staphylococcal enterotoxin A and E (SEA and SEE) can activate a large number of T-cells. SEA and SEE have approximately 80% sequence identity but show some differences in their biological function. Here, the two superantigens and analogues were characterized biophysically. SEE was shown to have a substantially higher thermal stability than SEA. Both SEA and SEE were thermally stabilized by 0.1 mM Zn(2+) compared with Zn(2+)-reduced conditions achieved using 1 mM EDTA or specific replacements that affect Zn(2+) coordination. The higher stability of SEE was only partly caused by the T-cell receptor (TCR) binding regions, whereas regions in the vicinity of the major histocompatibility complex class II binding sites affected the stability to a greater extent. SEE exhibited a biphasic denaturation between pH 5.0-6.5, influenced by residues in the TCR binding regions. Interestingly, enzyme-linked immunosorbent assay, isoelectric focusing, and circular dichroism analysis indicated that conformational changes had occurred in the SEA/E chimerical constructs relative to SEA and SEE. Thus, it is proposed that the Zn(2+) binding site is very important for the stability and potency of SEA and SEE, whereas residues in the TCR binding site have a substantial influence on the molecular conformation to control specificity and function. Study holds ProTherm entries: 6416, 6417, 6418, 6419, 6420, 6421, 6422, 6423, 6424, 6425, 6426, 6427 Extra Details: specific replacement; TCR binding; conformational change

Submission Details

ID: Ti3rXf5d

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:32 p.m.

Version: 1

Publication Details
Cavallin A;Arozenius H;Kristensson K;Antonsson P;Otzen DE;Björk P;Forsberg G,J. Biol. Chem. (2000) The spectral and thermodynamic properties of staphylococcal enterotoxin A, E, and variants suggest that structural modifications are important to control their function. PMID:10636860
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1DYQ 2001-03-19 1.5 STAPHYLOCOCCAL ENTEROTOXIN A MUTANT VACCINE
1ESF 1996-07-11 1.9 STAPHYLOCOCCAL ENTEROTOXIN A
1I4G 2001-02-28 2.1 Crystal structure of Staphylococcal enterotoxin A mutant H187A with reduced Zn2+ affinity
5FKA 2016-05-25 2.4 Crystal structure of staphylococcal enterotoxin E in complex with a T cell receptor
4UDU 2015-06-24 2.5 Crystal structure of staphylococcal enterotoxin E in complex with a T cell receptor
1SXT 1997-11-19 2.7 STAPHYLOCOCCAL ENTEROTOXIN TYPE A (SEA) CO-CRYSTALLISED WITH ZINC
1I4H 2001-02-28 2.9 Crystal structure of Zn2+ soaked Staphylococcal enterotoxin A mutant H187A
5FK9 2016-05-25 3.1 Crystal structure of staphylococcal enterotoxin A F47A mutant in complex with a T cell receptor
1LO5 2002-12-18 3.2 Crystal structure of the D227A variant of Staphylococcal enterotoxin A in complex with human MHC class II

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Enterotoxin type A P0A0L1 ETXA_STAAW
100.0 Enterotoxin type A P0A0L2 ETXA_STAAU
100.0 Enterotoxin type E P12993 ETXE_STAAU