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PDBsum entry 1hqr

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protein ligands metals Protein-protein interface(s) links
Immune system PDB id
1hqr
Jmol
Contents
Protein chains
178 a.a. *
180 a.a. *
206 a.a. *
Ligands
VAL-HIS-PHE-PHE-
LYS-ASN-ILE-VAL-
THR-PRO
Metals
_ZN
* Residue conservation analysis
PDB id:
1hqr
Name: Immune system
Title: Crystal structure of a superantigen bound to the high- affinity, zinc-dependent site on mhc class ii
Structure: Hla-dr alpha chain. Chain: a. Synonym: dra 0101. Engineered: yes. Hla-dr beta chain. Chain: b. Synonym: drb5 0101. Engineered: yes. Myelin basic protein.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expressed in: escherichia coli. Expression_system_taxid: 562. Streptococcus pyogenes. Organism_taxid: 1314.
Biol. unit: Octamer (from PQS)
Resolution:
3.20Å     R-factor:   0.224     R-free:   0.288
Authors: Y.Li,H.Li,N.Dimasi,P.Schlievert,R.Mariuzza
Key ref:
Y.Li et al. (2001). Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II. Immunity, 14, 93. PubMed id: 11163233 DOI: 10.1016/S1074-7613(01)00092-9
Date:
19-Dec-00     Release date:   03-Jan-01    
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 ?
Q30154  (DRB5_HUMAN) -  HLA class II histocompatibility antigen, DR beta 5 chain
Seq:
Struc:
266 a.a.
180 a.a.
Protein chain
Pfam   ArchSchema ?
Q8NKX2  (SPEC_STRP8) -  Exotoxin type C
Seq:
Struc:
235 a.a.
206 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 

 

 
DOI no: 10.1016/S1074-7613(01)00092-9 Immunity 14:93 (2001)
PubMed id: 11163233  
 
 
Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II.
Y.Li, H.Li, N.Dimasi, J.K.McCormick, R.Martin, P.Schuck, P.M.Schlievert, R.A.Mariuzza.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
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]).
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.
 
  The above figures are reprinted by permission from Cell Press: Immunity (2001, 14, 93-0) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21502329 S.O.Ryan, J.A.Bonomo, F.Zhao, and B.A.Cobb (2011).
MHCII glycosylation modulates Bacteroides fragilis carbohydrate antigen presentation.
  J Exp Med, 208, 1041-1053.  
21388361 S.Y.Ko, H.B.Oh, Y.S.Heo, J.H.Jun, and O.J.Kwon (2011).
HLA-DRB1*13:99, a novel HLA-DRB1*13 allele identified by sequence-based typing.
  Tissue Antigens, 77, 343-344.  
21092020 Y.H.Sohn, H.B.Oh, Y.S.Heo, N.Park, and O.J.Kwon (2011).
Identification of a novel HLA-DRB1 allele, DRB1*11:95.
  Tissue Antigens, 77, 160-161.  
21087493 E.John, T.C.Laskow, W.J.Buchser, B.R.Pitt, P.H.Basse, L.H.Butterfield, P.Kalinski, and M.T.Lotze (2010).
Zinc in innate and adaptive tumor immunity.
  J Transl Med, 8, 118.  
19609675 Z.Lin, D.P.Kotler, P.M.Schlievert, and E.M.Sordillo (2010).
Staphylococcal enterocolitis: forgotten but not gone?
  Dig Dis Sci, 55, 1200-1207.  
17268555 B.Moza, A.K.Varma, R.A.Buonpane, P.Zhu, C.A.Herfst, M.J.Nicholson, A.K.Wilbuer, N.P.Seth, K.W.Wucherpfennig, J.K.McCormick, D.M.Kranz, and E.J.Sundberg (2007).
Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1.
  EMBO J, 26, 1187-1197.
PDB code: 2ij0
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.  
17166841 H.Li, Y.Zhao, Y.Guo, Z.Li, L.Eisele, and W.Mourad (2007).
Zinc induces dimerization of the class II major histocompatibility complex molecule that leads to cooperative binding to a superantigen.
  J Biol Chem, 282, 5991-6000.
PDB code: 2oje
17427250 M.M.Fernández, S.Bhattacharya, M.C.De Marzi, P.H.Brown, M.Kerzic, P.Schuck, R.A.Mariuzza, and E.L.Malchiodi (2007).
Superantigen natural affinity maturation revealed by the crystal structure of staphylococcal enterotoxin G and its binding to T-cell receptor Vbeta8.2.
  Proteins, 68, 389-402.  
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
16829512 M.M.Fernández, R.Guan, C.P.Swaminathan, E.L.Malchiodi, and R.A.Mariuzza (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.
PDB code: 2g9h
15691839 B.V.Geisbrecht, B.Y.Hamaoka, B.Perman, A.Zemla, and D.J.Leahy (2005).
The crystal structures of EAP domains from Staphylococcus aureus reveal an unexpected homology to bacterial superantigens.
  J Biol Chem, 280, 17243-17250.
PDB codes: 1yn3 1yn4 1yn5
16113251 D.D.Pless, G.Ruthel, E.K.Reinke, R.G.Ulrich, and S.Bavari (2005).
Persistence of zinc-binding bacterial superantigens at the surface of antigen-presenting cells contributes to the extreme potency of these superantigens as T-cell activators.
  Infect Immun, 73, 5358-5366.  
15784559 M.L.Peterson, K.Ault, M.J.Kremer, A.J.Klingelhutz, C.C.Davis, C.A.Squier, and P.M.Schlievert (2005).
The innate immune system is activated by stimulation of vaginal epithelial cells with Staphylococcus aureus and toxic shock syndrome toxin 1.
  Infect Immun, 73, 2164-2174.  
16079912 Y.Li, Y.Huang, J.Lue, J.A.Quandt, R.Martin, and R.A.Mariuzza (2005).
Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule.
  EMBO J, 24, 2968-2979.
PDB code: 1zgl
14559915 A.C.Papageorgiou, M.D.Baker, J.D.McLeod, S.K.Goda, C.N.Manzotti, D.M.Sansom, H.S.Tranter, and K.R.Acharya (2004).
Identification of a secondary zinc-binding site in staphylococcal enterotoxin C2. Implications for superantigen recognition.
  J Biol Chem, 279, 1297-1303.
PDB code: 1uns
15479236 M.C.De Marzí, M.M.Fernández, E.J.Sundberg, L.Molinero, N.W.Zwirner, A.S.Llera, R.A.Mariuzza, and E.L.Malchiodi (2004).
Cloning, expression and interaction of human T-cell receptors with the bacterial superantigen SSA.
  Eur J Biochem, 271, 4075-4083.  
15295110 M.D.Baker, I.Gendlina, C.M.Collins, and K.R.Acharya (2004).
Crystal structure of a dimeric form of streptococcal pyrogenic exotoxin A (SpeA1).
  Protein Sci, 13, 2285-2290.
PDB code: 1uup
14555655 R.C.Hillig, M.Hülsmeyer, W.Saenger, K.Welfle, R.Misselwitz, H.Welfle, C.Kozerski, A.Volz, B.Uchanska-Ziegler, and A.Ziegler (2004).
Thermodynamic and structural analysis of peptide- and allele-dependent properties of two HLA-B27 subtypes exhibiting differential disease association.
  J Biol Chem, 279, 652-663.
PDB code: 1jgd
14962388 Y.Zhao, Z.Li, S.J.Drozd, Y.Guo, W.Mourad, and H.Li (2004).
Crystal structure of Mycoplasma arthritidis mitogen complexed with HLA-DR1 reveals a novel superantigen fold and a dimerized superantigen-MHC complex.
  Structure, 12, 277-288.
PDB code: 1r5i
12756270 K.Gamerdinger, C.Moulon, D.R.Karp, J.Van Bergen, F.Koning, D.Wild, U.Pflugfelder, and H.U.Weltzien (2003).
A new type of metal recognition by human T cells: contact residues for peptide-independent bridging of T cell receptor and major histocompatibility complex by nickel.
  J Exp Med, 197, 1345-1353.  
12615898 L.Lu, J.Vollmer, C.Moulon, H.U.Weltzien, P.Marrack, and J.Kappler (2003).
Components of the ligand for a Ni++ reactive human T cell clone.
  J Exp Med, 197, 567-574.  
12676930 M.A.Langlois, Y.El Fakhry, and W.Mourad (2003).
Zinc-binding sites in the N terminus of Mycoplasma arthritidis-derived mitogen permit the dimer formation required for high affinity binding to HLA-DR and for T cell activation.
  J Biol Chem, 278, 22309-22315.  
12704169 P.M.Orwin, J.R.Fitzgerald, D.Y.Leung, J.A.Gutierrez, G.A.Bohach, and P.M.Schlievert (2003).
Characterization of Staphylococcus aureus enterotoxin L.
  Infect Immun, 71, 2916-2919.  
12595474 T.J.Tripp, J.K.McCormick, J.M.Webb, and P.M.Schlievert (2003).
The zinc-dependent major histocompatibility complex class II binding site of streptococcal pyrogenic exotoxin C is critical for maximal superantigen function and toxic activity.
  Infect Immun, 71, 1548-1550.  
12595453 T.Proft, P.D.Webb, V.Handley, and J.D.Fraser (2003).
Two novel superantigens found in both group A and group C Streptococcus.
  Infect Immun, 71, 1361-1369.  
12595587 T.Yoshioka, T.Matsutani, T.Toyosaki-Maeda, H.Suzuki, S.Uemura, R.Suzuki, M.Koike, and Y.Hinuma (2003).
Relation of streptococcal pyrogenic exotoxin C as a causative superantigen for Kawasaki disease.
  Pediatr Res, 53, 403-410.  
12473669 W.Swietnicki, A.M.Barnie, B.K.Dyas, and R.G.Ulrich (2003).
Zinc binding and dimerization of Streptococcus pyogenes pyrogenic exotoxin C are not essential for T-cell stimulation.
  J Biol Chem, 278, 9885-9895.  
  12234092 D.S.Libich, and G.Harauz (2002).
Interactions of the 18.5-kDa isoform of myelin basic protein with Ca(2+)-calmodulin: in vitro studies using fluorescence microscopy and spectroscopy.
  Biochem Cell Biol, 80, 395-406.  
11790531 E.J.Sundberg, Y.Li, and R.A.Mariuzza (2002).
So many ways of getting in the way: diversity in the molecular architecture of superantigen-dependent T-cell signaling complexes.
  Curr Opin Immunol, 14, 36-44.  
11847286 H.I.Krupka, B.W.Segelke, R.G.Ulrich, S.Ringhofer, M.Knapp, and B.Rupp (2002).
Structural basis for abrogated binding between staphylococcal enterotoxin A superantigen vaccine and MHC-IIalpha.
  Protein Sci, 11, 642-651.
PDB code: 1dyq
11864610 M.M.Mullen, K.M.Haan, R.Longnecker, and T.S.Jardetzky (2002).
Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II receptor HLA-DR1.
  Mol Cell, 9, 375-385.
PDB code: 1kg0
12082105 V.L.Arcus, R.Langley, T.Proft, J.D.Fraser, and E.N.Baker (2002).
The Three-dimensional structure of a superantigen-like protein, SET3, from a pathogenicity island of the Staphylococcus aureus genome.
  J Biol Chem, 277, 32274-32281.
PDB code: 1m4v
11934896 Y.I.Chi, I.Sadler, L.M.Jablonski, S.D.Callantine, C.F.Deobald, C.V.Stauffacher, and G.A.Bohach (2002).
Zinc-mediated dimerization and its effect on activity and conformation of staphylococcal enterotoxin type C.
  J Biol Chem, 277, 22839-22846.
PDB code: 1ck1
11432818 K.Petersson, M.Håkansson, H.Nilsson, G.Forsberg, L.A.Svensson, A.Liljas, and B.Walse (2001).
Crystal structure of a superantigen bound to MHC class II displays zinc and peptide dependence.
  EMBO J, 20, 3306-3312.
PDB code: 1hxy
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 code is shown on the right.