PDBsum entry 1eu3

Immune system

PDB id: 1eu3

Contents

Protein chains

210 a.a. *

Ligands

PO4 ×3

Metals

__K

_ZN ×2

Waters ×416

* Residue conservation analysis

PDB id:

1eu3

Name:

Immune system

Title:

Crystal structure of the superantigen smez-2 (zinc bound) from streptococcus pyogenes

Structure:

Superantigen smez-2. Chain: a, b. Engineered: yes

Source:

Streptococcus pyogenes. Organism_taxid: 1314. Strain: 2035. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.68Å R-factor: 0.207 R-free: 0.230

Authors:

V.L.Arcus,T.Proft,J.A.Sigrell,H.M.Baker,J.D.Fraser,E.N.Baker

Key ref:

V.L.Arcus et al. (2000). Conservation and variation in superantigen structure and activity highlighted by the three-dimensional structures of two new superantigens from Streptococcus pyogenes. J Mol Biol, 299, 157-168. PubMed id: 10860729 DOI: 10.1006/jmbi.2000.3725

Date:

13-Apr-00 Release date: 26-Apr-00

Protein chains

Q9RQQ5  (Q9RQQ5_STRPY) -  Mitogenic exotoxin Z 2 (Fragment) from Streptococcus pyogenes

Seq: 209 a.a.

Struc: 210 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1006/jmbi.2000.3725

J Mol Biol 299:157-168 (2000)

PubMed id: 10860729

Conservation and variation in superantigen structure and activity highlighted by the three-dimensional structures of two new superantigens from Streptococcus pyogenes.

V.L.Arcus, T.Proft, J.A.Sigrell, H.M.Baker, J.D.Fraser, E.N.Baker.

ABSTRACT

Bacterial superantigens (SAgs) are a structurally related group of protein toxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They are implicated in a range of human pathologies associated with bacterial infection whose symptoms result from SAg-mediated stimulation of a large number (2-20%) of T-cells. At the molecular level, bacterial SAgs bind to major histocompatability class II (MHC-II) molecules and disrupt the normal interaction between MHC-II and T-cell receptors (TCRs). We have determined high-resolution crystal structures of two newly identified streptococcal superantigens, SPE-H and SMEZ-2. Both structures conform to the generic bacterial superantigen folding pattern, comprising an OB-fold N-terminal domain and a beta-grasp C-terminal domain. SPE-H and SMEZ-2 also display very similar zinc-binding sites on the outer concave surfaces of their C-terminal domains. Structural comparisons with other SAgs identify two structural sub-families. Sub-families are related by conserved core residues and demarcated by variable binding surfaces for MHC-II and TCR. SMEZ-2 is most closely related to the streptococcal SAg SPE-C, and together they constitute one structural sub-family. In contrast, SPE-H appears to be a hybrid whose N-terminal domain is most closely related to the SEB sub-family and whose C-terminal domain is most closely related to the SPE-C/SMEZ-2 sub-family. MHC-II binding for both SPE-H and SMEZ-2 is mediated by the zinc ion at their C-terminal face, whereas the generic N-terminal domain MHC-II binding site found on many SAgs appears not to be present. Structural comparisons provide evidence for variations in TCR binding between SPE-H, SMEZ-2 and other members of the SAg family; the extreme potency of SMEZ-2 (active at 10(-15) g ml-1 levels) is likely to be related to its TCR binding properties. The smez gene shows allelic variation that maps onto a considerable proportion of the protein surface. This allelic variation, coupled with the varied binding modes of SAgs to MHC-II and TCR, highlights the pressure on SAgs to avoid host immune defences.

Selected figure(s)

Figure 1.
Figure 1. Polypeptide folding and binding sites for individual superantigens. For SMEZ-2 and SPE-H, zinc-binding residues and conserved residues on the MHC-II binding face are shown in grey. The bound zinc is shown as an orange sphere. For TSST and SEB, residues that interact with MHC-II are shown in grey and those that interact with the TCR are shown in yellow. TCR-binding residues are from structural data for SEB (Jardetzky et al., 1994) and mutational studies for TSST (Hurley et al., 1995).

Figure 4.
Figure 4. Invariant residues in superantigens. The majority of invariant residues across the SAg family form a hydrogen bonding or charge-charge network cross-link- ing a2, a4 and a5 and the intersec- tion of the two domains. This buried polar network is shown for SMEZ-2 and is representative of all the known bacterial SAg structures.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 299, 157-168) copyright 2000.

Figures were selected by the author.