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PDBsum entry 1hqr
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Immune system
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PDB id
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1hqr
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Contents |
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178 a.a.
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180 a.a.
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206 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of a superantigen bound to the high-Affinity, Zinc-Dependent site on mhc class ii.
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Authors
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Y.Li,
H.Li,
N.Dimasi,
J.K.Mccormick,
R.Martin,
P.Schuck,
P.M.Schlievert,
R.A.Mariuzza.
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Ref.
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Immunity, 2001,
14,
93.
[DOI no: ]
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PubMed id
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Abstract
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MHC class II molecules possess two binding sites for bacterial superantigens
(SAGs): a low-affinity site on the alpha chain and a high-affinity,
zinc-dependent site on the beta chain. Only the former has been defined
crystallographically. We report the structure of streptococcal pyrogenic
exotoxin C (SPE-C) complexed with HLA-DR2a (DRA*0101, DRB5*0101) bearing a
self-peptide from myelin basic protein (MBP). SPE-C binds the beta chain through
a zinc bridge that links the SAG and class II molecules. Surprisingly, SPE-C
also makes extensive contacts with the MBP peptide, such that peptide accounts
for one third of the surface area of the MHC molecule buried in the complex,
similar to TCR-peptide/MHC complexes. Thus, SPE-C may optimize T cell responses
by mimicking the peptide dependence of conventional antigen presentation and
recognition.
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Figure 4.
Figure 4. Comparison of the Docking Modes of SAGs and TCR
on MHC Class II(A) View of the HLA-DR2a/MBP/SPE-C complex
looking down into the peptide binding groove of the class II
molecule. The N terminus of the MBP peptide (pink) is at the
upper left. Colors are as follows: DR2a α1 domain, green; DR2a
β1 domain, light blue; and SPE-C, gray.(B) The complex between
TCR D10 (purple) and I-A^k bearing a conalbumin peptide ([48]).
The orientation of the class II molecule is the same as in
(A).(C) The complex between SEB (dark blue) and HLA-DR1
([25]).(D) The complex between TSST-1 (yellow) and HLA-DR1
([26]).
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Figure 5.
Figure 5. High-Affinity Binding Site of SEA and Model of
MHC Cross-Linking(A) Comparison of the high-affinity binding
sites of SPE-C and SEA for MHC class II. The region of unbound
SPE-C (gray) ([51]) containing the principal contact residues to
class II in the HLA-DR2a/MBP/SPE-C complex was superposed onto
the corresponding region of unbound SEA (orange) ( [52]). Side
chains of SPE-C that interact with MHC class II/peptide are
green; the corresponding side chains of SEA are red.(B) Model
of SEA cross-linking two MHC class II molecules. SEA is
orange, and the α and β chains of HLA-DR2a are green and light
blue, respectively. The peptides are pink, and the interface
zinc is a yellow sphere. The model was constructed by
least-squares superposition of (1) the HLA-DR2a/SPE-C complex,
(2) SEA ([52]), and (3) the HLA-DR1/SEB complex ( [25]). The C
termini of the class II α and β chains are labeled.
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The above figures are
reprinted
by permission from Cell Press:
Immunity
(2001,
14,
93-0)
copyright 2001.
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