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PDBsum entry 2g9h

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protein ligands metals Protein-protein interface(s) links
Immune system PDB id
2g9h
Jmol
Contents
Protein chains
178 a.a. *
190 a.a. *
13 a.a. *
213 a.a. *
Ligands
SO4 ×4
EPE
DIO ×2
Metals
_ZN
Waters ×460
* Residue conservation analysis
PDB id:
2g9h
Name: Immune system
Title: Crystal structure of staphylococcal enterotoxin i (sei) in c with a human mhc class ii molecule
Structure: Hla class ii histocompatibility antigen, dr alpha chain: a. Synonym: mhc class ii antigen dra. Engineered: yes. Hla class ii histocompatibility antigen, drb1-1 b chain: b. Synonym: mhc class i antigen drb1 1, Dr-1, dr1. Engineered: yes. Hemagglutinin.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-dra. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: hla-drb1. Synthetic: yes. Other_details: this sequence occurs nuturally in influenza
Biol. unit: Tetramer (from PQS)
Resolution:
2.00Å     R-factor:   0.215     R-free:   0.252
Authors: M.M.Fernandez,R.Guan,E.L.Malchiodi,R.A.Mariuzza
Key ref:
M.M.Fernández et al. (2006). Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule. J Biol Chem, 281, 25356-25364. PubMed id: 16829512 DOI: 10.1074/jbc.M603969200
Date:
06-Mar-06     Release date:   11-Jul-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain
Seq:
Struc:
254 a.a.
178 a.a.
Protein chain
Pfam   ArchSchema ?
P04229  (2B11_HUMAN) -  HLA class II histocompatibility antigen, DRB1-1 beta chain
Seq:
Struc:
266 a.a.
190 a.a.
Protein chain
Pfam   ArchSchema ?
P04664  (HEMA_I69A0) -  Hemagglutinin (Fragment)
Seq:
Struc:
328 a.a.
13 a.a.
Protein chain
Pfam   ArchSchema ?
Q52T95  (Q52T95_STAAU) -  Enterotoxin type I (Fragment)
Seq:
Struc:
218 a.a.
213 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     immune response   3 terms 
  Biochemical function     metal ion binding     1 term  

 

 
DOI no: 10.1074/jbc.M603969200 J Biol Chem 281:25356-25364 (2006)
PubMed id: 16829512  
 
 
Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule.
M.M.Fernández, R.Guan, C.P.Swaminathan, E.L.Malchiodi, R.A.Mariuzza.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
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.
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).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 25356-25364) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21081917 M.Saline, K.E.Rödström, G.Fischer, V.Y.Orekhov, B.G.Karlsson, and K.Lindkvist-Petersson (2010).
The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation.
  Nat Commun, 1, 119.
PDB codes: 2xn9 2xna
18946350 L.E.Morales-Buenrostro, P.I.Terasaki, L.A.Marino-Vázquez, J.H.Lee, N.El-Awar, and J.Alberú (2008).
"Natural" human leukocyte antigen antibodies found in nonalloimmunized healthy males.
  Transplantation, 86, 1111-1115.  
17560120 E.J.Sundberg, L.Deng, and R.A.Mariuzza (2007).
TCR recognition of peptide/MHC class II complexes and superantigens.
  Semin Immunol, 19, 262-271.  
17560605 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, and E.J.Sundberg (2007).
A novel loop domain in superantigens extends their T cell receptor recognition site.
  J Mol Biol, 371, 210-221.
PDB codes: 2nts 2ntt
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.