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PDBsum entry 2g9h
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Immune system
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PDB id
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2g9h
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Contents |
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178 a.a.
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190 a.a.
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13 a.a.
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213 a.a.
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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 staphylococcal enterotoxin i (sei) in complex with a human major histocompatibility complex class ii molecule.
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Authors
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M.M.Fernández,
R.Guan,
C.P.Swaminathan,
E.L.Malchiodi,
R.A.Mariuzza.
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Ref.
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J Biol Chem, 2006,
281,
25356-25364.
[DOI no: ]
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PubMed id
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Abstract
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Superantigens are bacterial or viral proteins that elicit massive T cell
activation through simultaneous binding to major histocompatibility complex
(MHC) class II and T cell receptors. This activation results in uncontrolled
release of inflammatory cytokines, causing toxic shock. A remarkable property of
superantigens, which distinguishes them from T cell receptors, is their ability
to interact with multiple MHC class II alleles independently of MHC-bound
peptide. Previous crystallographic studies have shown that staphylococcal and
streptococcal superantigens belonging to the zinc family bind to a high affinity
site on the class II beta-chain. However, the basis for promiscuous MHC
recognition by zinc-dependent superantigens is not obvious, because the
beta-chain is polymorphic and the MHC-bound peptide forms part of the binding
interface. To understand how zinc-dependent superantigens recognize MHC, we
determined the crystal structure, at 2.0 A resolution, of staphylococcal
enterotoxin I bound to the human class II molecule HLA-DR1 bearing a peptide
from influenza hemagglutinin. Interactions between the superantigen and DR1
beta-chain are mediated by a zinc ion, and 22% of the buried surface of
peptide.MHC is contributed by the peptide. Comparison of the staphylococcal
enterotoxin I.peptide.DR1 structure with ones determined previously revealed
that zinc-dependent superantigens achieve promiscuous binding to MHC by
targeting conservatively substituted residues of the polymorphic beta-chain.
Additionally, these superantigens circumvent peptide specificity by engaging
MHC-bound peptides at their conformationally conserved N-terminal regions while
minimizing sequence-specific interactions with peptide residues to enhance
cross-reactivity.
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Figure 2.
FIGURE 2. Structure of the  4- 5 loop of SEI. A,
electron density from the final 2F[o] – F[c] map at 2.0
Å resolution showing SEI residues 70–75 in a stick
representation. Carbon atoms are green, nitrogen atoms are blue,
oxygen atoms are red, and the sulfur atom is yellow. B,
superposition of SEI (cyan) onto SPEC (red) in the SPEC·V
2.1
structure (38). Steric clashes are observed between the 4- 5 loop of
SEI (blue) and CDR1 (yellow) and CDR2 (brown) of V 2.1. CDR3
is purple; hypervariable region 4 (HV4) and framework region 3
(FR3) are green. The 4- 5 loop of SPEC is pink.
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Figure 4.
FIGURE 4. Interactions in the SEI·HA·DR1,
SEH·HA·DR1, and SPEC·MBP·DR2a
interfaces. A, interactions between the HLA-DR1 -chain
(blue) and SEI (yellow) in the SEI·HA·DR1 complex.
The DR1  -chain (green) does not
contact SEI. Residues of the DR1 -chain involved in
interactions with SEI are green. The interface zinc ion is drawn
as a red sphere. Hydrogen bonds are represented as dashed lines.
Oxygen and nitrogen atoms are colored red and blue,
respectively. B, interactions between the HA peptide (pink) and
SEI (yellow). Peptide residues P–1 Lys and P2 Val (purple)
contact the SAG. C, Zn^2+ coordination in the
SEI·HA·DR1 complex. The zinc ion is tetrahedrally
coordinated by SEI residues His^169, His^207, and Asp^209
(yellow) and by HLA-DR1 residue His^81 (green). D, interactions
between the HLA-DR1 -chain (blue) and SEH
(yellow) in the SEH·HA·DR1 complex. Residues
Asp-55 and Asn^57 of the
DR1 -chain (green) also
contact SEH. E, interactions between the HA peptide (pink) and
SEH (yellow). Peptide residues P–1 Lys and P3 Lys (purple)
contact the SAG. F, Zn^2+ coordination in the
SEH·HA·DR1 complex. The zinc ion is coordinated by
SEH residues His^206 and Asp^208 (yellow) and by DR1 residue
His^81 (green). G, interactions
between the HLA-DR2a -chain (blue) and SPEC
(yellow) in the SPEC·MBP·DR2a complex. The DR2a
-chain (green) does not
contact SPEC. H, interactions between the MBP peptide (pink) and
SPEC (yellow). Peptide residues P–3 Val, P–2 His, P–1 Phe,
P2 Lys, and P3 Asn (purple) contact the SAG. I, Zn^2+
coordination in the SPEC·MBP·DR2a complex. The
zinc ion is coordinated tetrahedrally by SPEC residues His^167,
His^201, and Asp^203 (yellow) and by HLA-DR2a residue His^81
(green).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
25356-25364)
copyright 2006.
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