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PDBsum entry 2nna

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protein Protein-protein interface(s) links
Immune system PDB id
2nna
Jmol
Contents
Protein chains
182 a.a. *
182 a.a. *
13 a.a. *
Waters ×311
* Residue conservation analysis
PDB id:
2nna
Name: Immune system
Title: Structure of the mhc class ii molecule hla-dq8 bound with a gluten peptide
Structure: Mhc class ii antigen. Chain: a. Fragment: residues in database 24-207. Engineered: yes. Mhc class ii antigen. Chain: b. Fragment: residues in database 33-224. Engineered: yes. Gluten peptide.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic: yes. Other_details: thE C terminus of chain c was linked to the terminus of chain b with a flexible serine glycine linker. Flexible linker was cleaved with trypsin at an unknown poin
Resolution:
2.10Å     R-factor:   0.217     R-free:   0.248
Authors: K.N.Henderson,J.A.Tye-Din,J.Rossjohn,R.P.Anderson
Key ref: K.N.Henderson et al. (2007). A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease. Immunity, 27, 23-34. PubMed id: 17629515
Date:
24-Oct-06     Release date:   04-Sep-07    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01909  (DQA1_HUMAN) -  HLA class II histocompatibility antigen, DQ alpha 1 chain
Seq:
Struc:
254 a.a.
182 a.a.*
Protein chain
Pfam   ArchSchema ?
P01920  (DQB1_HUMAN) -  HLA class II histocompatibility antigen, DQ beta 1 chain
Seq:
Struc:
261 a.a.
182 a.a.*
Protein chain
No UniProt id for this chain
Struc: 13 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 23 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     immune response   2 terms 

 

 
Immunity 27:23-34 (2007)
PubMed id: 17629515  
 
 
A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease.
K.N.Henderson, J.A.Tye-Din, H.H.Reid, Z.Chen, N.A.Borg, T.Beissbarth, A.Tatham, S.I.Mannering, A.W.Purcell, N.L.Dudek, D.A.van Heel, J.McCluskey, J.Rossjohn, R.P.Anderson.
 
  ABSTRACT  
 
The risk of celiac disease is strongly associated with human leukocyte antigen (HLA) DQ2 and to a lesser extent with HLA DQ8. Although the pathogenesis of HLA-DQ2-mediated celiac disease is established, the underlying basis for HLA-DQ8-mediated celiac disease remains unclear. We showed that T helper 1 (Th1) responses in HLA-DQ8-associated celiac pathology were indeed HLA DQ8 restricted and that multiple, mostly deamidated peptides derived from protease-sensitive sites of gliadin were recognized. This pattern of reactivity contrasted with the more absolute deamidation dependence and relative protease resistance of the dominant gliadin peptide in DQ2-mediated disease. We provided a structural basis for the selection of HLA-DQ8-restricted, deamidated gliadin peptides. The data established that the molecular mechanisms underlying HLA-DQ8-mediated celiac disease differed markedly from the HLA-DQ2-mediated form of the disease. Accordingly, nondietary therapeutic interventions in celiac disease might need to be tailored to the genotype of the individual.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21443726 E.D.Newnham (2011).
Does gluten cause gastrointestinal symptoms in subjects without coeliac disease?
  J Gastroenterol Hepatol, 26, 132-134.  
21224837 J.R.Biesiekierski, E.D.Newnham, P.M.Irving, J.S.Barrett, M.Haines, J.D.Doecke, S.J.Shepherd, J.G.Muir, and P.R.Gibson (2011).
Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.
  Am J Gastroenterol, 106, 508-514.  
21219178 V.Abadie, L.M.Sollid, L.B.Barreiro, and B.Jabri (2011).
Integration of genetic and immunological insights into a model of celiac disease pathogenesis.
  Annu Rev Immunol, 29, 493-525.  
20661732 J.M.Tjon, J.van Bergen, and F.Koning (2010).
Celiac disease: how complicated can it get?
  Immunogenetics, 62, 641-651.  
20190752 P.C.Dubois, G.Trynka, L.Franke, K.A.Hunt, J.Romanos, A.Curtotti, A.Zhernakova, G.A.Heap, R.Adány, A.Aromaa, M.T.Bardella, L.H.van den Berg, N.A.Bockett, E.G.de la Concha, B.Dema, R.S.Fehrmann, M.Fernández-Arquero, S.Fiatal, E.Grandone, P.M.Green, H.J.Groen, R.Gwilliam, R.H.Houwen, S.E.Hunt, K.Kaukinen, D.Kelleher, I.Korponay-Szabo, K.Kurppa, P.MacMathuna, M.Mäki, M.C.Mazzilli, O.T.McCann, M.L.Mearin, C.A.Mein, M.M.Mirza, V.Mistry, B.Mora, K.I.Morley, C.J.Mulder, J.A.Murray, C.Núñez, E.Oosterom, R.A.Ophoff, I.Polanco, L.Peltonen, M.Platteel, A.Rybak, V.Salomaa, J.J.Schweizer, M.P.Sperandeo, G.J.Tack, G.Turner, J.H.Veldink, W.H.Verbeek, R.K.Weersma, V.M.Wolters, E.Urcelay, B.Cukrowska, L.Greco, S.L.Neuhausen, R.McManus, D.Barisani, P.Deloukas, J.C.Barrett, P.Saavalainen, C.Wijmenga, and D.A.van Heel (2010).
Multiple common variants for celiac disease influencing immune gene expression.
  Nat Genet, 42, 295-302.  
20616724 S.A.Leddon, and A.J.Sant (2010).
Generation of MHC class II-peptide ligands for CD4 T-cell allorecognition of MHC class II molecules.
  Curr Opin Organ Transplant, 15, 505-511.  
19935805 B.Jabri, and L.M.Sollid (2009).
Tissue-mediated control of immunopathology in coeliac disease.
  Nat Rev Immunol, 9, 858-870.  
19461125 K.Y.Chang, and E.R.Unanue (2009).
Prediction of HLA-DQ8beta cell peptidome using a computational program and its relationship to autoreactive T cells.
  Int Immunol, 21, 705-713.  
19718029 L.E.Fallang, E.Bergseng, K.Hotta, A.Berg-Larsen, C.Y.Kim, and L.M.Sollid (2009).
Differences in the risk of celiac disease associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation.
  Nat Immunol, 10, 1096-1101.  
19017300 S.Caillat-Zucman (2009).
Molecular mechanisms of HLA association with autoimmune diseases.
  Tissue Antigens, 73, 1-8.  
19342211 S.W.Qiao, L.M.Sollid, and R.S.Blumberg (2009).
Antigen presentation in celiac disease.
  Curr Opin Immunol, 21, 111-117.  
18549801 D.Chessman, L.Kostenko, T.Lethborg, A.W.Purcell, N.A.Williamson, Z.Chen, L.Kjer-Nielsen, N.A.Mifsud, B.D.Tait, R.Holdsworth, C.A.Almeida, D.Nolan, W.A.Macdonald, J.K.Archbold, A.D.Kellerher, D.Marriott, S.Mallal, M.Bharadwaj, J.Rossjohn, and J.McCluskey (2008).
Human leukocyte antigen class I-restricted activation of CD8+ T cells provides the immunogenetic basis of a systemic drug hypersensitivity.
  Immunity, 28, 822-832.
PDB code: 2rfx
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.  
18957072 D.R.Lester (2008).
Gluten measurement and its relationship to food toxicity for celiac disease patients.
  Plant Methods, 4, 26.  
18799120 J.Tye-Din, and R.Anderson (2008).
Immunopathogenesis of celiac disease.
  Curr Gastroenterol Rep, 10, 458-465.  
18537178 R.A.Harris, K.Sugimoto, D.E.Kaplan, F.Ikeda, M.Kamoun, and K.M.Chang (2008).
Human leukocyte antigen class II associations with hepatitis C virus clearance and virus-specific CD4 T cell response among Caucasians and African Americans.
  Hepatology, 48, 70-79.  
19037317 Z.Hovhannisyan, A.Weiss, A.Martin, M.Wiesner, S.Tollefsen, K.Yoshida, C.Ciszewski, S.A.Curran, J.A.Murray, C.S.David, L.M.Sollid, F.Koning, L.Teyton, and B.Jabri (2008).
The role of HLA-DQ8 beta57 polymorphism in the anti-gluten T-cell response in coeliac disease.
  Nature, 456, 534-538.  
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.