PDBsum entry 1ty2

Immune system

PDB id: 1ty2

Contents

Protein chains

211 a.a. *

Metals

_ZN ×3

Waters ×159

* Residue conservation analysis

PDB id:

1ty2

Name:

Immune system

Title:

Crystal structure of the streptococcal pyrogenic exotoxin j (spe-j)

Structure:

Putative exotoxin (superantigen). Chain: a, b, c. Synonym: exotoxin j, spe-j. Engineered: yes

Source:

Streptococcus pyogenes. Organism_taxid: 1314. Gene: spe-j. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Not given

Resolution:

2.00Å R-factor: 0.218 R-free: 0.249

Authors:

H.M.Baker,T.Proft,P.D.Webb,V.L.Arcus,J.D.Fraser,E.N.Baker

Key ref:

H.M.Baker et al. (2004). Crystallographic and mutational data show that the streptococcal pyrogenic exotoxin J can use a common binding surface for T-cell receptor binding and dimerization. J Biol Chem, 279, 38571-38576. PubMed id: 15247241 DOI: 10.1074/jbc.M406695200

Date:

07-Jul-04 Release date: 17-Aug-04

Protein chains

Q7BAE3  (Q7BAE3_STRPY) -  Exotoxin J from Streptococcus pyogenes

Seq: 232 a.a.

Struc: 211 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M406695200

J Biol Chem 279:38571-38576 (2004)

PubMed id: 15247241

Crystallographic and mutational data show that the streptococcal pyrogenic exotoxin J can use a common binding surface for T-cell receptor binding and dimerization.

H.M.Baker, T.Proft, P.D.Webb, V.L.Arcus, J.D.Fraser, E.N.Baker.

ABSTRACT

The protein toxins known as superantigens (SAgs), which are expressed primarily by the pathogenic bacteria Staphylococcus aureus and Streptococcus pyogenes, are highly potent immunotoxins with the ability to cause serious human disease. These SAgs share a conserved fold but quite varied activities. In addition to their common role of cross-linking T-cell receptors (TCRs) and major histocompatibility complex class II (MHC-II) molecules, some SAgs can cross-link MHC-II, using diverse mechanisms. The crystal structure of the streptococcal superantigen streptococcal pyrogenic exotoxin J (SPE-J) has been solved at 1.75 A resolution (R = 0.209, R(free) = 0.240), both with and without bound Zn(2+). The structure displays the canonical two-domain SAg fold and a zinc-binding site that is shared by a subset of other SAgs. Most importantly, in concentrated solution and in the crystal, SPE-J forms dimers. These dimers, which are present in two different crystal environments, form via the same face that is used for TCR binding in other SAgs. Site-directed mutagenesis shows that this face is also used for TCR binding SPE-J. We infer that SPE-J cross-links TCR and MHC-II as a monomer but that dimers may form on the antigen-presenting cell surface, cross-linking MHC-II and eliciting intracellular signaling.

Selected figure(s)

Figure 1.
FIG. 1. Structure of the SpeJ monomer. Ribbon diagram in which the major secondary structural elements are labeled in accord with the nomenclature first used for SEB (42). In this orientation the N-terminal domain is on the right and the C-terminal domain on the left. Secondary structural elements are as follows: 2, 2-19; 1, 21-32; 2, 35-40; 3, 48-54; 4, 66-72; 5a, 81-87; 5b, 88-92; 6, 102-108; 7, 111-118; 8, 125-127; 4, 128-145; 9, 155-162; 10, 166-172; 5, 180-186; 11, 194-196; and 12, 201-208. Figure was drawn with Pymol.

Figure 2.
FIG. 2. Dimerization of SpeJ. Stereo view of the SPE-J dimer, with the two molecules shown in blue and yellow. Side chains that make significant contributions to the dimer interface are shown in red, with the major contributors labeled: Y, Tyr-14; I, Ile-19; F, Phe-77; and R, Arg-181. The C-terminal domain in each monomer provides the binding site for the zinc ion (gray sphere) that binds to MHC-II. Fig. drawn with MOLSCRIPT (43) and rendered with RASTER3D (44).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 38571-38576) copyright 2004.

Figures were selected by the author.