spacer
spacer

PDBsum entry 3fol

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Immune system PDB id
3fol
Jmol
Contents
Protein chains
274 a.a. *
100 a.a. *
Ligands
VAL-ASN-ASP-ILE-
PHE-GLU-ARG-ILE
Waters ×65
* Residue conservation analysis
PDB id:
3fol
Name: Immune system
Title: Crystal structure of the class i mhc molecule h-2kwm7 with a self peptide vndiferi
Structure: Mhc. Chain: a. Engineered: yes. Beta-2-microglobulin. Chain: b. Fragment: igc. Engineered: yes. 8 residue synthetic peptide. Chain: p.
Source: Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m. Synthetic: yes. Other_details: the peptide was chemically synthesized. It i naturally in mouse.
Resolution:
2.50Å     R-factor:   0.196     R-free:   0.261
Authors: D.R.Brims,J.Qian,I.Jarchum,T.Yamada,L.Mikesh,E.Palmieri,T.Lu M.Hattori,J.Shabanowitz,D.F.Hunt,U.A.Ramagopal,V.N.Malashke S.C.Almo,S.G.Nathenson,T.P.Dilorenzo
Key ref: D.R.Brims et al. (2010). Predominant occupation of the class I MHC molecule H-2Kwm7 with a single self-peptide suggests a mechanism for its diabetes-protective effect. Int Immunol, 22, 191-203. PubMed id: 20093428
Date:
30-Dec-08     Release date:   12-Jan-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
D2YW38  (D2YW38_MOUSE) -  MHC
Seq:
Struc:
274 a.a.
274 a.a.
Protein chain
Pfam   ArchSchema ?
P01887  (B2MG_MOUSE) -  Beta-2-microglobulin
Seq:
Struc:
119 a.a.
100 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   10 terms 
  Biological process     immune system process   13 terms 
  Biochemical function     protein binding     3 terms  

 

 
Int Immunol 22:191-203 (2010)
PubMed id: 20093428  
 
 
Predominant occupation of the class I MHC molecule H-2Kwm7 with a single self-peptide suggests a mechanism for its diabetes-protective effect.
D.R.Brims, J.Qian, I.Jarchum, L.Mikesh, E.Palmieri, U.A.Ramagopal, V.N.Malashkevich, R.J.Chaparro, T.Lund, M.Hattori, J.Shabanowitz, D.F.Hunt, S.G.Nathenson, S.C.Almo, T.P.Dilorenzo.
 
  ABSTRACT  
 
Type 1 diabetes (T1D) is an autoimmune disease characterized by T cell-mediated destruction of insulin-producing pancreatic beta cells. In both humans and the non-obese diabetic (NOD) mouse model of T1D, class II MHC alleles are the primary determinant of disease susceptibility. However, class I MHC genes also influence risk. These findings are consistent with the requirement for both CD4(+) and CD8(+) T cells in the pathogenesis of T1D. Although a large body of work has permitted the identification of multiple mechanisms to explain the diabetes-protective effect of particular class II MHC alleles, studies examining the protective influence of class I alleles are lacking. Here, we explored this question by performing biochemical and structural analyses of the murine class I MHC molecule H-2K(wm7), which exerts a diabetes-protective effect in NOD mice. We have found that H-2K(wm7) molecules are predominantly occupied by the single self-peptide VNDIFERI, derived from the ubiquitous protein histone H2B. This unexpected finding suggests that the inability of H-2K(wm7) to support T1D development could be due, at least in part, to the failure of peptides from critical beta-cell antigens to adequately compete for binding and be presented to T cells. Predominant presentation of a single peptide would also be expected to influence T-cell selection, potentially leading to a reduced ability to select a diabetogenic CD8(+) T-cell repertoire. The report that one of the predominant peptides bound by T1D-protective HLA-A*31 is histone derived suggests the potential translation of our findings to human diabetes-protective class I MHC molecules.