Structure of Staphylococcal Enterotoxin N: Implications for Binding Properties to Its Cellular Proteins.

Zeng Zeng,Han Han,Liu Liu

doi:10.3390/ijms20235921

Abstract

Staphylococcus aureus strains produce a unique family of immunostimulatory exotoxins termed as bacterial superantigens (SAgs), which cross-link major histocompatibility complex class II (MHC II) molecule and T-cell receptor (TCR) to stimulate large numbers of T cells at extremely low concentrations. SAgs are associated with food poisoning and toxic shock syndrome. To date, 26 genetically distinct staphylococcal SAgs have been reported. This study reports the first X-ray structure of newly characterized staphylococcal enterotoxin N (SEN). SEN possesses the classical two domain architecture that includes an N-terminal oligonucleotide-binding fold and a C-terminal β-grasp domain. Amino acid and structure alignments revealed that several critical amino acids that are proposed to be responsible for MHC II and TCR molecule engagements are variable in SEN, suggesting that SEN may adopt a different binding mode to its cellular receptors. This work helps better understand the mechanisms of action of SAgs.

Highlights

Superantigens (SAgs) are the critical virulence factors of Staphylococcus aureus [1,2]
The structure of staphylococcal enterotoxin N (SEN) was solved by molecular replacement, and the final model was refined at 1.8 Å resolution (Rwork = 0.171, Rfree = 0.201, Table 1)
Residues 27–51 from the N-terminal of SEN encompass one side of the β-grasp domain with α2 in this region situated in the middle of the two domains. α2, α4, and α5 form an approximate triangle

Summary

Introduction

Superantigens (SAgs) are the critical virulence factors of Staphylococcus aureus [1,2]. Mature SAgs have a relatively low molecular weight of 19,000–30,000 Da (220–240 amino acids) [2,3]. More than 26 genetically distinct staphylococcal SAgs have been described, including TSS toxin-1 (TSST-1), staphylococcal enterotoxins (SEs), and SE-like (SE-l) SAgs [5,6,7,8]. SE-type superantigens are defined by their ability to induce emesis, and SE-l-type either lack of emetic activity or have not been formally investigated to induce emesis [9]. Staphylococcal SAgs are categorized based on their amino acid sequence divergence into four evolutionary groups: I, II, III, and V (SAg group IV is streptococcal exotoxins)

Methods

Results

Conclusion