Limits...
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

Presentation of the buried surface areas in the SEE-TCR interface.(A) The areas in the TRBV domain which are buried upon binding are marked in colors corresponding to the CDR1 loop (red), CDR2 loop (green), FR3 region (blue), HV4 loop (purple) and FR4 region (orange). (B) The buried surface area in SEE is marked in colors corresponding to the α2-helix and following loop (purple), the hydrophobic patch consisting of the β2-β3 (green) and β4-β5a (blue) loops, the α4-β9 loop (red), and the upper part of the α5-helix (orange).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4492778&req=5

pone.0131988.g002: Presentation of the buried surface areas in the SEE-TCR interface.(A) The areas in the TRBV domain which are buried upon binding are marked in colors corresponding to the CDR1 loop (red), CDR2 loop (green), FR3 region (blue), HV4 loop (purple) and FR4 region (orange). (B) The buried surface area in SEE is marked in colors corresponding to the α2-helix and following loop (purple), the hydrophobic patch consisting of the β2-β3 (green) and β4-β5a (blue) loops, the α4-β9 loop (red), and the upper part of the α5-helix (orange).

Mentions: The T cell receptor recognizes SEE using its TRBV domain by binding to a shallow groove between the N- and C-terminal domains of SEE. The interface buries a dual surface area of 1945 Å2, with main contributions from the CDR2 loop (38.4%), the FR3 region (24.3%) and the HV4 loop (20.8%), as well as smaller contributions from the CDR1 loop (8.4%) and FR4 region (8.1%), whereas there are no contacts to the CDR3 loop of TRBV (Fig 2A). There are 16 hydrogen bonds present (Fig 1, S2 Table), and Van der Waals contacts (≤ 4.0 Å) are made with 23 residues in TCR and 19 in SEE (S3 Table). There are four major TCR-contacting points in the SAg: the α2-helix, the hydrophobic patch consisting of the β2-β3 and β4-β5a loops, the α4-β9 loop, and the upper part of the α5-helix (Fig 1 and Fig 2B). Residue Asn25s, located in the α2-helix, which also is important for T cell activation in other superantigens [45–47], forms two hydrogen bonds to the backbone of Gln55b in the CDR2 loop (Fig 1B). In addition, residues Asn21s, Arg27s, and Gln28s, also in the α2-helix, form hydrogen bonds to CDR2 and HV4 (Fig 1B). Interestingly, five out of eight hydrogen bonds from the α2-helix are to the backbone of the TCR (Fig 1B, S2 Table). The hydrophobic patch consists of Gly93s and Tyr94s in the β4-β5a loop, and is extended with residues Trp63s and Tyr64s in the β2-β3 loop. In particular, Trp63s packs against the CDR1, 2 and HV4 loops and contributes alone to 14% of the buried surface area of SEE (Fig 1C). In contrast to the α2-helix of SEE, the hydrophobic patch forms hydrogen bonds mostly to side chain atoms of TRBV, for instance by Tyr64s and Gly93s to the CDR2 loop (Fig 1C). Another feature of the SEE-TCR interface is the α4-β9 loop, which packs against the upper parts of the FR3 and FR4 regions. Here, Phe175s contributes with 13% to the buried surface area in SEE, and Ser174s forms a hydrogen bond to the side chain of Gln81b (Fig 1D). Lastly, the N-terminal part of helix α5 is also involved in the interface, utilizing residues Tyr205s and Pro206s, where a hydrogen bond is formed by Tyr205s to the main chain of Leu56b in FR3 (Fig 1E).


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)

Presentation of the buried surface areas in the SEE-TCR interface.(A) The areas in the TRBV domain which are buried upon binding are marked in colors corresponding to the CDR1 loop (red), CDR2 loop (green), FR3 region (blue), HV4 loop (purple) and FR4 region (orange). (B) The buried surface area in SEE is marked in colors corresponding to the α2-helix and following loop (purple), the hydrophobic patch consisting of the β2-β3 (green) and β4-β5a (blue) loops, the α4-β9 loop (red), and the upper part of the α5-helix (orange).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131988.g002: Presentation of the buried surface areas in the SEE-TCR interface.(A) The areas in the TRBV domain which are buried upon binding are marked in colors corresponding to the CDR1 loop (red), CDR2 loop (green), FR3 region (blue), HV4 loop (purple) and FR4 region (orange). (B) The buried surface area in SEE is marked in colors corresponding to the α2-helix and following loop (purple), the hydrophobic patch consisting of the β2-β3 (green) and β4-β5a (blue) loops, the α4-β9 loop (red), and the upper part of the α5-helix (orange).
Mentions: The T cell receptor recognizes SEE using its TRBV domain by binding to a shallow groove between the N- and C-terminal domains of SEE. The interface buries a dual surface area of 1945 Å2, with main contributions from the CDR2 loop (38.4%), the FR3 region (24.3%) and the HV4 loop (20.8%), as well as smaller contributions from the CDR1 loop (8.4%) and FR4 region (8.1%), whereas there are no contacts to the CDR3 loop of TRBV (Fig 2A). There are 16 hydrogen bonds present (Fig 1, S2 Table), and Van der Waals contacts (≤ 4.0 Å) are made with 23 residues in TCR and 19 in SEE (S3 Table). There are four major TCR-contacting points in the SAg: the α2-helix, the hydrophobic patch consisting of the β2-β3 and β4-β5a loops, the α4-β9 loop, and the upper part of the α5-helix (Fig 1 and Fig 2B). Residue Asn25s, located in the α2-helix, which also is important for T cell activation in other superantigens [45–47], forms two hydrogen bonds to the backbone of Gln55b in the CDR2 loop (Fig 1B). In addition, residues Asn21s, Arg27s, and Gln28s, also in the α2-helix, form hydrogen bonds to CDR2 and HV4 (Fig 1B). Interestingly, five out of eight hydrogen bonds from the α2-helix are to the backbone of the TCR (Fig 1B, S2 Table). The hydrophobic patch consists of Gly93s and Tyr94s in the β4-β5a loop, and is extended with residues Trp63s and Tyr64s in the β2-β3 loop. In particular, Trp63s packs against the CDR1, 2 and HV4 loops and contributes alone to 14% of the buried surface area of SEE (Fig 1C). In contrast to the α2-helix of SEE, the hydrophobic patch forms hydrogen bonds mostly to side chain atoms of TRBV, for instance by Tyr64s and Gly93s to the CDR2 loop (Fig 1C). Another feature of the SEE-TCR interface is the α4-β9 loop, which packs against the upper parts of the FR3 and FR4 regions. Here, Phe175s contributes with 13% to the buried surface area in SEE, and Ser174s forms a hydrogen bond to the side chain of Gln81b (Fig 1D). Lastly, the N-terminal part of helix α5 is also involved in the interface, utilizing residues Tyr205s and Pro206s, where a hydrogen bond is formed by Tyr205s to the main chain of Leu56b in FR3 (Fig 1E).

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