PDBsum entry 2ian

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protein Protein-protein interface(s) links
Immune system PDB id
Protein chains
178 a.a. *
181 a.a. *
15 a.a. *
198 a.a. *
238 a.a. *
Waters ×76
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Structural basis for recognition of mutant self by a tumor- specific, mhc class ii-restricted tcr
Structure: Hla class ii histocompatibility antigen, dr alpha chain. Chain: a, f, k, p. Fragment: residues 1-182 (26-207). Synonym: mhc class ii antigen dra, major histocompatibility complex class ii hla-dr1 alpha chain. Engineered: yes. Hla class ii histocompatibility antigen, drb1-1 beta chain.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-dra. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Gene: hla-drb1. Gene: tpi1, tpi.
2.80Å     R-factor:   0.225     R-free:   0.296
Authors: L.Deng,R.J.Langley,R.A.Mariuzza
Key ref:
L.Deng et al. (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. PubMed id: 17334368 DOI: 10.1038/ni1447
08-Sep-06     Release date:   03-Apr-07    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain
254 a.a.
178 a.a.
Protein chains
Pfam   ArchSchema ?
P04229  (2B11_HUMAN) -  HLA class II histocompatibility antigen, DRB1-1 beta chain
266 a.a.
181 a.a.
Protein chains
Pfam   ArchSchema ?
P60174  (TPIS_HUMAN) -  Triosephosphate isomerase
286 a.a.
15 a.a.
Protein chains
Pfam   ArchSchema ?
P01848  (TCA_HUMAN) -  T-cell receptor alpha chain C region
142 a.a.
198 a.a.*
Protein chains
Pfam   ArchSchema ?
P01850  (TRBC1_HUMAN) -  T-cell receptor beta-1 chain C region
177 a.a.
238 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains C, H, M, R: 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     membrane   2 terms 
  Biological process     immune response   2 terms 


    Added reference    
DOI no: 10.1038/ni1447 Nat Immunol 8:398-408 (2007)
PubMed id: 17334368  
Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor.
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, R.A.Mariuzza.
Structural studies of complexes of T cell receptor (TCR) and peptide-major histocompatibility complex (MHC) have focused on TCRs specific for foreign antigens or native self. An unexplored category of TCRs includes those specific for self determinants bearing alterations resulting from disease, notably cancer. We determined here the structure of a human melanoma-specific TCR (E8) bound to the MHC molecule HLA-DR1 and an epitope from mutant triosephosphate isomerase. The structure had features intermediate between 'anti-foreign' and autoimmune TCR-peptide-MHC class II complexes that may reflect the hybrid nature of altered self. E8 manifested very low affinity for mutant triosephosphate isomerase-HLA-DR1 despite the highly tumor-reactive properties of E8 cells. A second TCR (G4) had even lower affinity but underwent peptide-specific formation of dimers, suggesting this as a mechanism for enhancing low-affinity TCR-peptide-MHC interactions for T cell activation.
  Selected figure(s)  
Figure 4.
(a) TCR residues in contact with mutant TPI. The substituted TPI isoleucine residue (position 3) is magenta. (b) Interactions between E8 and mutant TPI. (c) Interactions between the E8 V[ ]domain and the HLA-DR1 1 -helix. (d,e) Interactions between mutant TPI isoleucine at position 3 and TCR E8 (d) or wild-type TPI threonine at position 3 and HLA-DR1 complexes (e). TCR residues are identified by one-letter amino-acid designation followed by position number and chain designation; peptide residues are identified by one-letter amino-acid designation followed by position ('P') number. Colors of TCR and MHC molecules as in Figure 3; hydrogen bonds, red dotted lines; salt bridges, solid lines; van der Waals contacts, black dotted lines.
Figure 6.
(a–c) Structural rearrangements in CDR2 , CDR3 and CDR3 induced by binding to mutant TPI–DR1. Bound E8, green; unbound E8, magenta; HLA-DR1, gold; mutant TPI, gray. Residues from E8 and DR1 involved in interactions with peptide are identified. (d) Superposition of mutant TPI–DR1 in a form without bound ligand (peptide, cyan; MHC, violet) and in complex with E8 (peptide, gray; MHC, gold). Arrow indicates residues 55–59 of the HLA-DR1 1 domain. (e) Conformational changes in TPI residues that contact E8. Residues of TPI involved in interactions with E8 are identified. Residue designations as in Figure 4.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Immunol (2007, 8, 398-408) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21364947 J.M.Khan, and S.Ranganathan (2011).
Understanding TR Binding to pMHC Complexes: How Does a TR Scan Many pMHC Complexes yet Preferentially Bind to One.
  PLoS One, 6, e17194.  
19806353 P.Schuck (2010).
On computational approaches for size-and-shape distributions from sedimentation velocity analytical ultracentrifugation.
  Eur Biophys J, 39, 1261-1275.  
20334923 S.P.Persaud, D.L.Donermeyer, K.S.Weber, D.M.Kranz, and P.M.Allen (2010).
High-affinity T cell receptor differentiates cognate peptide-MHC and altered peptide ligands with distinct kinetics and thermodynamics.
  Mol Immunol, 47, 1793-1801.  
19759824 G.Chen, G.Han, J.Feng, J.Wang, R.Wang, R.Xu, B.Shen, J.Qian, and Y.Li (2009).
Glutamic acid decarboxylase-derived epitopes with specific domains expand CD4(+)CD25(+) regulatory T cells.
  PLoS One, 4, e7034.  
19699075 K.W.Wucherpfennig, M.J.Call, L.Deng, and R.Mariuzza (2009).
Structural alterations in peptide-MHC recognition by self-reactive T cell receptors.
  Curr Opin Immunol, 21, 590-595.  
19303388 M.Harkiolaki, S.L.Holmes, P.Svendsen, J.W.Gregersen, L.T.Jensen, R.McMahon, M.A.Friese, G.van Boxel, R.Etzensperger, J.S.Tzartos, K.Kranc, S.Sainsbury, K.Harlos, E.D.Mellins, J.Palace, M.M.Esiri, P.A.van der Merwe, E.Y.Jones, and L.Fugger (2009).
T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides.
  Immunity, 30, 348-357.
PDB code: 2wbj
19464197 T.Beddoe, Z.Chen, C.S.Clements, L.K.Ely, S.R.Bushell, J.P.Vivian, L.Kjer-Nielsen, S.S.Pang, M.A.Dunstone, Y.C.Liu, W.A.Macdonald, M.A.Perugini, M.C.Wilce, S.R.Burrows, A.W.Purcell, T.Tiganis, S.P.Bottomley, J.McCluskey, and J.Rossjohn (2009).
Antigen ligation triggers a conformational change within the constant domain of the alphabeta T cell receptor.
  Immunity, 30, 777-788.  
18342005 D.I.Godfrey, J.Rossjohn, and J.McCluskey (2008).
The fidelity, occasional promiscuity, and versatility of T cell receptor recognition.
  Immunity, 28, 304-314.  
18800968 K.M.Armstrong, K.H.Piepenbrink, and B.M.Baker (2008).
Conformational changes and flexibility in T-cell receptor recognition of peptide-MHC complexes.
  Biochem J, 415, 183-196.  
18304006 P.Marrack, J.P.Scott-Browne, S.Dai, L.Gapin, and J.W.Kappler (2008).
Evolutionarily conserved amino acids that control TCR-MHC interaction.
  Annu Rev Immunol, 26, 171-203.  
18456484 P.Marrack, K.Rubtsova, J.Scott-Browne, and J.W.Kappler (2008).
T cell receptor specificity for major histocompatibility complex proteins.
  Curr Opin Immunol, 20, 203-207.  
17521918 C.Mazza, and B.Malissen (2007).
What guides MHC-restricted TCR recognition?
  Semin Immunol, 19, 225-235.  
17950605 L.Deng, and R.A.Mariuzza (2007).
Recognition of self-peptide-MHC complexes by autoimmune T-cell receptors.
  Trends Biochem Sci, 32, 500-508.  
17960150 M.E.Call, and K.W.Wucherpfennig (2007).
Common themes in the assembly and architecture of activating immune receptors.
  Nat Rev Immunol, 7, 841-850.  
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.