PDBsum entry 2ntt

Toxin

PDB id: 2ntt

Contents

Protein chains

217 a.a. *

Ligands

EDO ×10

Metals

_CL ×13

Waters ×706

* Residue conservation analysis

PDB id:

2ntt

Name:

Toxin

Title:

Crystal structure of sek

Structure:

Staphylococcal enterotoxin k. Chain: a, b. Engineered: yes

Source:

Staphylococcus aureus subsp. Aureus. Organism_taxid: 93062. Strain: col. Gene: sek. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.56Å R-factor: 0.165 R-free: 0.202

Authors:

S.Gunther,A.K.Varma,B.Moza,E.J.Sundberg

Key ref:

S.Günther et al. (2007). A novel loop domain in superantigens extends their T cell receptor recognition site. J Mol Biol, 371, 210-221. PubMed id: 17560605 DOI: 10.1016/j.jmb.2007.05.038

Date:

08-Nov-06 Release date: 26-Jun-07

Protein chains

Q93CC5  (Q93CC5_STAAU) -  Sek from Staphylococcus aureus

Seq: 242 a.a.

Struc: 217 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.jmb.2007.05.038

J Mol Biol 371:210-221 (2007)

PubMed id: 17560605

A novel loop domain in superantigens extends their T cell receptor recognition site.

S.Günther, A.K.Varma, B.Moza, K.J.Kasper, A.W.Wyatt, P.Zhu, A.K.Rahman, Y.Li, R.A.Mariuzza, J.K.McCormick, E.J.Sundberg.

ABSTRACT

Superantigens (SAGs) interact with host immune receptors to induce a massive release of inflammatory cytokines that can lead to toxic shock syndrome and death. Bacterial SAGs can be classified into five distinct evolutionary groups. Group V SAGs are characterized by the alpha3-beta8 loop, a unique approximately 15 amino acid residue extension that is required for optimal T cell activation. Here, we report the X-ray crystal structures of the group V SAG staphylococcal enterotoxin K (SEK) alone and in complex with the TCR hVbeta5.1 domain. SEK adopts a unique TCR binding orientation relative to other SAG-TCR complexes, which results in the alpha3-beta8 loop contacting the apical loop of framework region 4, thereby extending the known TCR recognition site of SAGs. These interactions are absolutely required for TCR binding and T cell activation by SEK, and dictate the TCR Vbeta domain specificity of SEK and other group V SAGs.

Selected figure(s)

Figure 1.
Figure 1. Structural similarity of SEK and other group V bacterial superantigens. (a) Structure of SEK in the unbound state. The α3-β8 loop is in orange and the residues responsible for Zn^2+ coordination and MHC class II binding are in cyan. (b) Structural comparison of the α3-β8 loop domains of SEK, SEI and SpeI. Superposition of the main chains of the α3-β8 loops (left-hand panel). Molecular details of side-chain positions in the α3-β8 loops (right-hand panels). SEK, SEI and SpeI are in magenta, green and blue, respectively. The residues in SEK that interact with TCR, His142 and Tyr158, as well as corresponding residues in SEI and SpeI are encircled. (c) Structural comparison of the MHC binding site of SEI and the putative MHC binding sites of SEK and SpeI. Superposition of SEK and SpeI with SEI from the SEI-MHC class II crystal structure (left-hand panel).^21 Close-up view of the Zn^2+ coordination between SEI residues His169, His207 and Asp209 and the MHC β subunit residue His81 (middle panel). Close-up views of the putative SAG-MHC interface formed by the superposed SEK and SpeI structures (right-hand panels). The MHC α subunit is in yellow, the MHC β subunit is in red, the zinc ion is in gray, and the SAG colors are as in (b).

Figure 5.
Figure 5. MHC-SAG-TCR ternary signaling complexes mediated by (a) TSST-1, (b) SEB, (c) SpeC, and (d) SEK. Colors are as follows: MHC α subunit, green; MHC β subunit, blue; antigenic peptide, gray; TCR α chain, orange; TCR β chain, red; SAGs, yellow. For clarity, the MHC-SAG-TCR complexes mediated by (c) SpeC and (d) SEK are rotated approximately 90° clockwise about the vertical axis of the page relative to those mediated by (a) TSST-1 and (b) SEB.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 371, 210-221) copyright 2007.

Figures were selected by an automated process.