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PDBsum entry 1es0

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protein Protein-protein interface(s) links
Immune system PDB id
1es0
Jmol
Contents
Protein chains
182 a.a. *
190 a.a. *
Waters ×76
* Residue conservation analysis
PDB id:
1es0
Name: Immune system
Title: Crystal structure of the murine class ii allele i-a(g7) comp the glutamic acid decarboxylase (gad65) peptide 207-220
Structure: H-2 class ii histocompatibility antigen. Chain: a. Fragment: alpha chain. Engineered: yes. 65 kd glutamic acid decarboxylase+h-2 class ii histocompatibility antigen. Chain: b. Fragment: peptide (residues 222-235) + beta chain. Engineered: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Homo sapiens. Human. Organism_taxid: 9606.
Biol. unit: Tetramer (from PQS)
Resolution:
2.60Å     R-factor:   0.210     R-free:   0.258
Authors: A.L.Corper,L.Teyton,I.A.Wilson
Key ref:
A.L.Corper et al. (2000). A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes. Science, 288, 505-511. PubMed id: 10775108 DOI: 10.1126/science.288.5465.505
Date:
07-Apr-00     Release date:   28-Jun-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04228  (HA2D_MOUSE) -  H-2 class II histocompatibility antigen, A-D alpha chain
Seq:
Struc:
256 a.a.
182 a.a.*
Protein chain
Pfam   ArchSchema ?
Q05329  (DCE2_HUMAN) -  Glutamate decarboxylase 2
Seq:
Struc:
 
Seq:
Struc:
585 a.a.
190 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 170 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain B: E.C.4.1.1.15  - Glutamate decarboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-glutamate = 4-aminobutanoate + CO2
L-glutamate
= 4-aminobutanoate
+ CO(2)
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-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 

 

 
    reference    
 
 
DOI no: 10.1126/science.288.5465.505 Science 288:505-511 (2000)
PubMed id: 10775108  
 
 
A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes.
A.L.Corper, T.Stratmann, V.Apostolopoulos, C.A.Scott, K.C.Garcia, A.S.Kang, I.A.Wilson, L.Teyton.
 
  ABSTRACT  
 
Susceptibility to murine and human insulin-dependent diabetes mellitus correlates strongly with major histocompatibility complex (MHC) class II I-A or HLA-DQ alleles that lack an aspartic acid at position beta57. I-Ag7 lacks this aspartate and is the only class II allele expressed by the nonobese diabetic mouse. The crystal structure of I-Ag7 was determined at 2.6 angstrom resolution as a complex with a high-affinity peptide from the autoantigen glutamic acid decarboxylase (GAD) 65. I-Ag7 has a substantially wider peptide-binding groove around beta57, which accounts for distinct peptide preferences compared with other MHC class II alleles. Loss of Asp(beta57) leads to an oxyanion hole in I-Ag7 that can be filled by peptide carboxyl residues or, perhaps, through interaction with the T cell receptor.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Structure analysis of I-A^g7-GAD[207-220 ]and comparison with other murine MHC class II alleles. (A) Cross-validated [A]-weighted 2F[o] F[c] electron density of the GAD[207-220] peptide. The map, contoured at 1 , represents the final refined structure. Electron density for the peptide main-chain atoms is present for residues P 2 to P12; however, convincing side-chain density for Tyr-207 (P 2), Tyr-218 (P10), and Thr-220 (P12) was absent (59). The side chains for these residues were therefore truncated back to C[ ]. Final coordinates are overlaid in the map. (B) Overlay of the murine MHC class II molecules I-A^g7 (red), I-A^d (yellow, green), and I-A^k (blue). The C[ ]trace (22) shows only the [1] and [1] domain of the respective MHC II molecule. The two I-A^d pMHC complexes are colored green (peptide OVA[323-339]; PDB code 1IAO) and yellow (peptide HA[126-138]; PDB code 2IAD), respectively. The peptide COOH- and NH[2]-termini are respectively labeled N- and C-. The peptide core (P1 to P9) overlays well in all four structures. (C) Key residues that differ in I-A^g7 around the P9 pocket, their effect on peptide presentation, and the position of H1 and H2a segments of the [1]-chain[ ]helices. The polymorphic residues His 56, Ser 57, and Tyr 61 (H1) are found in I-A^g7, but not in other I-A alleles. The presence of Ser 57, in place of the highly conserved Asp 57, substantially alters the specificity of the P9 pocket. The orientation of the Tyr 61 side chain plays a significant role in the displacement of the H1 helical segment; the side-chain phenyl ring is almost perpendicular to that observed for the indole of the corresponding Trp residue in I-A^d,k. Displacement of the [1]H1 helical segment allows the side chain of Tyr 61 to be accommodated and dramatically alters the shape of the P9 pocket. (D) Unique character of the I-A^g7 P9 pocket. The presence of Ser 57 in I-A^g7, coupled with displacement of the H1 helix away from the peptide groove, increases the lateral freedom for the P9 peptide side chain, as clearly seen from a comparison of I-A^g7 (red) with I-A^d (cyan), I-A^k (green), I-E^k (gold), HLA-DR1 (purple and blue), and HLA-DR3 (yellow). The P9 side chains for all except I-A^g7 point downward in a classical manner. Three other MHC class II molecules are not shown: HLA-DR1 [PDB code 1SEB (60)] was built with a polyalanine peptide. HLA-DR2 is unusual in that the P9 side chain points toward the side of the peptide groove rather than downward in the classical manner. This orientation occurs as a result of an elevated COOH-terminus of the peptide and suboptimal occupancy of the P9 pocket, because the pocket itself is identical to that found in HLA-DR1 (61). HLA-DR4 [PDB code 2SEB (62)] has a glycine at P9. Stereo versions of Fig. 2, B and C, are available from Science Online as Web figure 1 (21).
Figure 4.
Fig. 4. Comparison of the peptide specificity pockets of (A) I-A^g7 and (B) I-A^d . Molecular surfaces were calculated with a probe radius of 1.4 Å (64). The peptides are in spacefilling (CPK) representation (backbone, yellow; side chain, dark blue). Waters, rendered as spheres of one-half van der Waals (VDW) radii, are colored red. The P1, P4, and P6 pockets of I-A^g7 and I-A^d (15) are about the same size, whereas the P9 pocket of I-A^d is larger but lacks the additional side cavity. I-A^g7 appears to maintain some conformational flexibility in defining the shape of the P1 pocket; repositioning of Leu 31 and Trp 43, compared with the analogous residues in I-A^d, allows the P1 pocket to be occupied by the Ile-209 side chain (and three water molecules).
 
  The above figures are reprinted by permission from the AAAs: Science (2000, 288, 505-511) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

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PDB codes: 3fol 3fom 3fon
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PDB codes: 1fzj 1fzk 1fzm 1fzo
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Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1.
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PDB code: 1fyt
10894169 R.R.Latek, A.Suri, S.J.Petzold, C.A.Nelson, O.Kanagawa, E.R.Unanue, and D.H.Fremont (2000).
Structural basis of peptide binding and presentation by the type I diabetes-associated MHC class II molecule of NOD mice.
  Immunity, 12, 699-710.
PDB code: 1f3j
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Animal models of autoimmunity and their relevance to human diseases.
  Curr Opin Immunol, 12, 684-690.  
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.