PDBsum entry 1klg

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protein Protein-protein interface(s) links
Immune system/toxin PDB id
Jmol PyMol
Protein chains
177 a.a. *
187 a.a. *
15 a.a. *
231 a.a. *
Waters ×275
* Residue conservation analysis
PDB id:
Name: Immune system/toxin
Title: Crystal structure of hla-dr1/tpi(23-37, thr28-->ile mutant) complexed with staphylococcal enterotoxin c3 variant 3b2 (sec3-3b2)
Structure: Hla class ii histocompatibility antigen, dr alpha chain. Chain: a. Fragment: residues 29-205. Synonym: hla-dr1 alpha subunit. Hla-dr antigen alpha chain. Engineered: yes. Hla class ii histocompatibility antigen, dr-1 beta chain. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: peptide synthesis. Staphylococcus aureus. Organism_taxid: 1280.
Biol. unit: Dodecamer (from PQS)
2.40Å     R-factor:   0.206     R-free:   0.246
Authors: E.J.Sundberg,M.W.Sawicki,P.S.Andersen,J.Sidney,A.Sette, R.A.Mariuzza
Key ref:
E.J.Sundberg et al. (2002). Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4+ tumor-infiltrating lymphocyte line. J Mol Biol, 319, 449-461. PubMed id: 12051920 DOI: 10.1016/S0022-2836(02)00370-4
11-Dec-01     Release date:   02-Aug-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain
254 a.a.
177 a.a.
Protein chain
Pfam   ArchSchema ?
P04229  (2B11_HUMAN) -  HLA class II histocompatibility antigen, DRB1-1 beta chain
266 a.a.
187 a.a.
Protein chain
Pfam   ArchSchema ?
P60174  (TPIS_HUMAN) -  Triosephosphate isomerase
286 a.a.
15 a.a.*
Protein chain
Pfam   ArchSchema ?
P0A0L5  (ENTC3_STAAU) -  Enterotoxin type C-3
266 a.a.
231 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain C: E.C.  - Triose-phosphate isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: D-glyceraldehyde 3-phosphate = glycerone phosphate
D-glyceraldehyde 3-phosphate
= glycerone phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     immune response   3 terms 


    Added reference    
DOI no: 10.1016/S0022-2836(02)00370-4 J Mol Biol 319:449-461 (2002)
PubMed id: 12051920  
Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4+ tumor-infiltrating lymphocyte line.
E.J.Sundberg, M.W.Sawicki, S.Southwood, P.S.Andersen, A.Sette, R.A.Mariuzza.
While most immunotherapies for cancer have focused on eliciting specific CD8+ cytotoxic T lymphocyte killing of tumor cells, a mounting body of evidence suggests that stimulation of anti-tumor CD4+ T cell help may be required for highly effective therapy. Several MHC class II-restricted tumor antigens that specifically activate such CD4+ helper T lymphocytes have now been identified, including one from a melanoma tumor that is caused by a single base-pair mutation in the glycolytic enzyme triosephosphate isomerase. This mutation results in the conversion of a threonine residue to isoleucine within the antigenic epitope, concomitant with a greater than five log-fold increase in stimulation of a CD4+ tumor-infiltrating lymphocyte line. Here, we present the crystal structures of HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first structures of tumor peptide antigen/MHC class II complexes recognized by CD4+ T cells to be reported. These structures show that very minor changes in the binding surface for T cell receptor correspond to the dramatic differences in T cell stimulation. Defining the structural basis by which CD4+ T cell help is invoked in an anti-tumor immune response will likely aid the design of more effective cancer immunotherapies.
  Selected figure(s)  
Figure 1.
Figure 1. The wild-type and mutant TPI[23-37] peptide/HLA-DR1/SEC3-3B2 complex structures. s[A]-Weighted 2F[o] -F[c] electron density maps in which the TPI[23-37] peptide atoms have been omitted from the map calculation for (a) the wild-type TPI[23-37] peptide and (b) the mutant TPI[23-37] peptide. Maps are contoured at 1.0s. (c) Superposition of the overall wild-type and mutant TPI[23-37] peptide/HLA-DR1/SEC3-3B2 complex structures. In all panels, colors are as follows: wild-type TPI[23-37] peptide, yellow; mutant TPI[23-37] peptide, green; HLA-DR1 a chain, purple; HLA-DR1 b chain, cyan; SEC3-3B2, red; nitrogen atoms, blue; oxygen atoms and water molecules, red. (a) and (b) produced using Bobscript[61] and Raster3D. [62] (c) and subsequent Figures produced using MOLSCRIPT [63] and Raster3D, [62] unless otherwise noted.
Figure 4.
Figure 4. Very similar molecular surfaces are presented to the T cell receptor by HLA-DR1 complexed with both the wild-type and mutant TPI[23-37] peptides. Molecular surface of HLA-DR1 complexed with (a) the wild-type TPI[23-37] peptide and (b) the mutant TPI[23-37] peptide. Color coding is as follows: green, carbon atoms; magenta, uncharged polar atoms; red, electronegative atoms; blue, electropositive atoms. The mutation site is outlined in black. Figure produced using GRASP.[64]
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 319, 449-461) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20657836 B.Knapp, U.Omasits, W.Schreiner, and M.M.Epstein (2010).
A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.
  PLoS One, 5, e11653.  
17512214 F.Song (2007).
A study of noncovalent protein complexes by matrix-assisted laser desorption/ionization.
  J Am Soc Mass Spectrom, 18, 1286-1290.  
17937498 J.M.Calvo-Calle, I.Strug, M.D.Nastke, S.P.Baker, and L.J.Stern (2007).
Human CD4+ T cell epitopes from vaccinia virus induced by vaccination or infection.
  PLoS Pathog, 3, 1511-1529.  
17334368 L.Deng, R.J.Langley, P.H.Brown, G.Xu, L.Teng, Q.Wang, M.I.Gonzales, G.G.Callender, M.I.Nishimura, S.L.Topalian, and R.A.Mariuzza (2007).
Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor.
  Nat Immunol, 8, 398-408.
PDB codes: 2ial 2iam 2ian
17022099 S.Y.Huang, Y.H.Chen, S.H.Teng, I.C.Chen, L.L.Ho, and C.F.Tu (2006).
Protein expression of lymphocytes in HLA-DR transgenic pigs by a proteomic approach.
  Proteomics, 6, 5815-5825.  
15049778 K.Petersson, G.Forsberg, and B.Walse (2004).
Interplay between superantigens and immunoreceptors.
  Scand J Immunol, 59, 345-355.  
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
14871288 S.H.Chang, J.Kim, K.Y.Lee, H.J.Kim, Y.J.Chung, C.U.Park, B.S.Kim, and Y.S.Jang (2004).
Modification of the inhibitory amino acid for epitope peptide binding onto major histocompatibility complex class II molecules enhances immunogenicity of the antigen.
  Scand J Immunol, 59, 123-132.  
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
15489166 Z.Zavala-Ruiz, I.Strug, M.W.Anderson, J.Gorski, and L.J.Stern (2004).
A polymorphic pocket at the P10 position contributes to peptide binding specificity in class II MHC proteins.
  Chem Biol, 11, 1395-1402.
PDB codes: 1t5w 1t5x
12952957 Z.Zavala-Ruiz, E.J.Sundberg, J.D.Stone, D.B.DeOliveira, I.C.Chan, J.Svendsen, R.A.Mariuzza, and L.J.Stern (2003).
Exploration of the P6/P7 region of the peptide-binding site of the human class II major histocompatability complex protein HLA-DR1.
  J Biol Chem, 278, 44904-44912.
PDB code: 1pyw
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.