PDBsum entry 1sxt

Superantigen

PDB id: 1sxt

Contents

Protein chains

224 a.a. *

Metals

_ZN ×2

* Residue conservation analysis

PDB id:

1sxt

Name:

Superantigen

Title:

Staphylococcal enterotoxin type a (sea) co-crystallised with zinc

Structure:

Staphylococcal enterotoxin type a. Chain: a, b. Synonym: sea. Engineered: yes

Source:

Staphylococcus aureus. Organism_taxid: 1280. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.70Å R-factor: 0.206 R-free: 0.317

Authors:

S.M.Sundstrom

Key ref:

M.Sundström et al. (1996). The Co-crystal structure of staphylococcal enterotoxin type A with Zn2+ at 2.7 A resolution. Implications for major histocompatibility complex class II binding. J Biol Chem, 271, 32212-32216. PubMed id: 8943278 DOI: 10.1074/jbc.271.50.32212

Date:

14-Nov-96 Release date: 19-Nov-97

Protein chains

P0A0L2  (ETXA_STAAU) -  Enterotoxin type A from Staphylococcus aureus

Seq: 257 a.a.

Struc: 224 a.a.

DOI no: 10.1074/jbc.271.50.32212

J Biol Chem 271:32212-32216 (1996)

PubMed id: 8943278

The Co-crystal structure of staphylococcal enterotoxin type A with Zn2+ at 2.7 A resolution. Implications for major histocompatibility complex class II binding.

M.Sundström, D.Hallén, A.Svensson, E.Schad, M.Dohlsten, L.Abrahmsén.

ABSTRACT

Superantigens form complexes with major histocompatibility complex (MHC) class II molecules and T-cell receptors resulting in extremely strong immunostimulatory properties. Staphylococcus aureus enterotoxin A (SEA) belongs to a subgroup of the staphylococcal superantigens that utilizes Zn2+ in the high affinity interaction with MHC class II molecules. A high affinity metal binding site was described previously in SEA co-crystallized with Cd2+ in which the metal ion was octahedrally co-ordinated, involving the N-terminal serine. We have now co-crystallized SEA with its native co-factor Zn2+ and determined its crystal structure at 2.7 A resolution. As expected for a Zn2+ ion, the co-ordination was found to be tetrahedral. Three of the ligands are located on the SEA surface on a C-terminal domain beta-sheet, while the fourth varies with the conditions. Further analysis of the zinc binding event was performed using titration microcalorimetry, which showed that SEA binds Zn2+ with an affinity of KD = 0.3 microM in an entropy driven process. The differential Zn2+ co-ordination observed here has implications for the mechanism of the SEA-MHC class II interaction.

Selected figure(s)

Figure 1.
Fig. 1. A representative part of the 2F[o]F[c] electron density map of SEA-Zn2+ in the core of the superantigen molecule. Observe the interactions between tyrosine residues that possibly contribute to the resistance^ of SEA to environmental factors such as high temperature or protease^ degradation. The 2F[o]F[c] electron density map is contoured at 1.2^ above the mean.

Figure 3.
Fig. 3. The zinc binding site of SEA co-crystallized with Zn2+. A, tetrahedral zinc co-ordination in molecule one (yellow) in the asymmetric unit. Note that the use of His61 from the neighboring molecule (cyan) as zinc ligand leads to the loop 59-63, absent in the SEA-Cd^2+ structure, here becoming ordered. B, tetrahedral zinc co-ordination in the second molecule of the asymmetric unit. The three high affinity SEA ligands are used and in addition a water molecule^ (H[2]O) is used as the fourth Zn2+ ligand. The figures were drawn using Molscript (30) and Raster3D^ (31).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1996, 271, 32212-32216) copyright 1996.

Figures were selected by an automated process.