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PDBsum entry 2ntt
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References listed in PDB file
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Key reference
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Title
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A novel loop domain in superantigens extends their t cell receptor recognition site.
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Authors
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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.
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Ref.
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J Mol Biol, 2007,
371,
210-221.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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).
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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.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
371,
210-221)
copyright 2007.
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