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Structure of Staphylococcal Enterotoxin E in Complex with TCR Defines the Role of TCR Loop Positioning in Superantigen Recognition.

Rödström KE, Regenthal P, Lindkvist-Petersson K - PLoS ONE (2015)

Bottom Line: Here, we present the structure of staphylococcal enterotoxin E (SEE) in complex with a human T cell receptor, as well as the unligated T cell receptor structure.In particular, the HV4 loop moves to circumvent steric clashes upon complex formation.In addition, a predicted ternary model of SEE in complex with both TCR and MHC class II displays intermolecular contacts between the TCR α-chain and the MHC, suggesting that the TCR α-chain is of importance for complex formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, Lund University, BMC C13, 22 184, Lund, Sweden.

ABSTRACT
T cells are crucial players in cell-mediated immunity. The specificity of their receptor, the T cell receptor (TCR), is central for the immune system to distinguish foreign from host antigens. Superantigens are bacterial toxins capable of inducing a toxic immune response by cross-linking the TCR and the major histocompatibility complex (MHC) class II and circumventing the antigen specificity. Here, we present the structure of staphylococcal enterotoxin E (SEE) in complex with a human T cell receptor, as well as the unligated T cell receptor structure. There are clear structural changes in the TCR loops upon superantigen binding. In particular, the HV4 loop moves to circumvent steric clashes upon complex formation. In addition, a predicted ternary model of SEE in complex with both TCR and MHC class II displays intermolecular contacts between the TCR α-chain and the MHC, suggesting that the TCR α-chain is of importance for complex formation.

No MeSH data available.


Related in: MedlinePlus

X-ray structure of the SEE-TCR complex.(A) Overall structure of the complex, with SEE in beige, the TCR α-chain in purple and the β-chain in blue. (B) Close-up of the SEE α2-helix and contacting residues in TCR, (C) the hydrophobic patch, (D) the α4-β9 loop, and (E) the upper part of the α5-helix. Hydrogen bonds are marked as dotted lines.
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pone.0131988.g001: X-ray structure of the SEE-TCR complex.(A) Overall structure of the complex, with SEE in beige, the TCR α-chain in purple and the β-chain in blue. (B) Close-up of the SEE α2-helix and contacting residues in TCR, (C) the hydrophobic patch, (D) the α4-β9 loop, and (E) the upper part of the α5-helix. Hydrogen bonds are marked as dotted lines.

Mentions: In order to study superantigen recognition by TCR, the structure of the TRAV22/TRBV7-9 TCR was determined in complex with staphylococcal enterotoxin E, to a resolution of 2.5 Å (Fig 1A). The complex crystallized in space group P212121 with one protein complex in the asymmetric unit. Data collection and refinement statistics are summarized in Table 1. The T cell receptor exhibited the same fold as described in the previous section, and the superantigen shares a similar fold with other bacterial superantigens, as first described for SEB [43]. SEE consists of two domains, an N-terminal domain resembling an oligosaccharide binding fold and a C-terminal β-grasp motif. The N-terminal domain consists of β-sheets (β1-β5) and a short α-helix (α3), and the C-terminal domain consists of an antiparallel β-sheet (β6, β7, β9, β10, and β12) packed against three α-helices (α2, α4 and α5), as well as a small two-stranded β-sheet (β8, β11). SEE is structurally and sequentially similar to SEA, with RMSD values between main chain atoms of 0.79 and 0.77 for the respective copies of SEA in the published three-dimensional structure (PDB ID: 1ESF) [16], and a sequence identity of 82%. In general, SEE engages the TRBV domain of TCR with the TCR binding site described for most other bacterial superantigens (Fig 1) [7, 44]. In the following paragraphs, residues will be designated a for TCRα, b for TCRβ, and s for SEE.


Structure of Staphylococcal Enterotoxin E in Complex with TCR Defines the Role of TCR Loop Positioning in Superantigen Recognition.

Rödström KE, Regenthal P, Lindkvist-Petersson K - PLoS ONE (2015)

X-ray structure of the SEE-TCR complex.(A) Overall structure of the complex, with SEE in beige, the TCR α-chain in purple and the β-chain in blue. (B) Close-up of the SEE α2-helix and contacting residues in TCR, (C) the hydrophobic patch, (D) the α4-β9 loop, and (E) the upper part of the α5-helix. Hydrogen bonds are marked as dotted lines.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492778&req=5

pone.0131988.g001: X-ray structure of the SEE-TCR complex.(A) Overall structure of the complex, with SEE in beige, the TCR α-chain in purple and the β-chain in blue. (B) Close-up of the SEE α2-helix and contacting residues in TCR, (C) the hydrophobic patch, (D) the α4-β9 loop, and (E) the upper part of the α5-helix. Hydrogen bonds are marked as dotted lines.
Mentions: In order to study superantigen recognition by TCR, the structure of the TRAV22/TRBV7-9 TCR was determined in complex with staphylococcal enterotoxin E, to a resolution of 2.5 Å (Fig 1A). The complex crystallized in space group P212121 with one protein complex in the asymmetric unit. Data collection and refinement statistics are summarized in Table 1. The T cell receptor exhibited the same fold as described in the previous section, and the superantigen shares a similar fold with other bacterial superantigens, as first described for SEB [43]. SEE consists of two domains, an N-terminal domain resembling an oligosaccharide binding fold and a C-terminal β-grasp motif. The N-terminal domain consists of β-sheets (β1-β5) and a short α-helix (α3), and the C-terminal domain consists of an antiparallel β-sheet (β6, β7, β9, β10, and β12) packed against three α-helices (α2, α4 and α5), as well as a small two-stranded β-sheet (β8, β11). SEE is structurally and sequentially similar to SEA, with RMSD values between main chain atoms of 0.79 and 0.77 for the respective copies of SEA in the published three-dimensional structure (PDB ID: 1ESF) [16], and a sequence identity of 82%. In general, SEE engages the TRBV domain of TCR with the TCR binding site described for most other bacterial superantigens (Fig 1) [7, 44]. In the following paragraphs, residues will be designated a for TCRα, b for TCRβ, and s for SEE.

Bottom Line: Here, we present the structure of staphylococcal enterotoxin E (SEE) in complex with a human T cell receptor, as well as the unligated T cell receptor structure.In particular, the HV4 loop moves to circumvent steric clashes upon complex formation.In addition, a predicted ternary model of SEE in complex with both TCR and MHC class II displays intermolecular contacts between the TCR α-chain and the MHC, suggesting that the TCR α-chain is of importance for complex formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, Lund University, BMC C13, 22 184, Lund, Sweden.

ABSTRACT
T cells are crucial players in cell-mediated immunity. The specificity of their receptor, the T cell receptor (TCR), is central for the immune system to distinguish foreign from host antigens. Superantigens are bacterial toxins capable of inducing a toxic immune response by cross-linking the TCR and the major histocompatibility complex (MHC) class II and circumventing the antigen specificity. Here, we present the structure of staphylococcal enterotoxin E (SEE) in complex with a human T cell receptor, as well as the unligated T cell receptor structure. There are clear structural changes in the TCR loops upon superantigen binding. In particular, the HV4 loop moves to circumvent steric clashes upon complex formation. In addition, a predicted ternary model of SEE in complex with both TCR and MHC class II displays intermolecular contacts between the TCR α-chain and the MHC, suggesting that the TCR α-chain is of importance for complex formation.

No MeSH data available.


Related in: MedlinePlus