PDBsum entry 1f3j

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Immune system PDB id
Protein chains
182 a.a. *
187 a.a. *
14 a.a. *
NAG ×6
Waters ×72
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Histocompatibility antigen i-ag7
Structure: H-2 class ii histocompatibility antigen. Chain: a, d. Fragment: a-d alpha chain. Engineered: yes. Mhc class ii nod. Chain: b, e. Fragment: beta chain. Engineered: yes. LysozymE C.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gallus gallus. Chicken. Organism_taxid: 9031.
Biol. unit: Trimer (from PQS)
3.10Å     R-factor:   0.221     R-free:   0.299
Authors: R.R.Latek,E.R.Unanue,D.H.Fremont
Key ref:
R.R.Latek et al. (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. PubMed id: 10894169 DOI: 10.1016/S1074-7613(00)80220-4
04-Jun-00     Release date:   20-Sep-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P04228  (HA2D_MOUSE) -  H-2 class II histocompatibility antigen, A-D alpha chain
256 a.a.
182 a.a.
Protein chains
Pfam   ArchSchema ?
Q31135  (Q31135_MOUSE) -  H2-Ab1 protein
263 a.a.
187 a.a.
Protein chains
Pfam   ArchSchema ?
P00698  (LYSC_CHICK) -  Lysozyme C
147 a.a.
14 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains P, Q: E.C.  - Lysozyme.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     immune response   2 terms 


DOI no: 10.1016/S1074-7613(00)80220-4 Immunity 12:699-710 (2000)
PubMed id: 10894169  
Structural basis of peptide binding and presentation by the type I diabetes-associated MHC class II molecule of NOD mice.
R.R.Latek, A.Suri, S.J.Petzold, C.A.Nelson, O.Kanagawa, E.R.Unanue, D.H.Fremont.
We have determined the crystal structure of I-Ag7, an integral component in murine type I diabetes development. Several features distinguish I-Ag7 from other non-autoimmune-associated MHC class II molecules, including novel peptide and heterodimer pairing interactions. The binding groove of I-Ag7 is unusual at both terminal ends, with a potentially solvent-exposed channel at the base of the P1 pocket and a widened entrance to the P9 pocket. Peptide binding studies with variants of the hen egg lysozyme I-Ag7 epitope HEL(11-25) support a comprehensive structure-based I-Ag7 binding motif. Residues critical for T cell recognition were investigated with a panel of HEL(11-25)-restricted clones, which uncovered P1 anchor-dependent structural variations. These results establish a framework for future experiments directed at understanding the role of I-Ag7 in autoimmunity.
  Selected figure(s)  
Figure 4.
Figure 4. I-A^g7 Pockets and Anchors(A) Molecular surface of I-A^g7 looking down into the peptide binding groove. Estimated electrostatic potentials were calculated in GRASP ([33]); positive potential (20 mv) colored blue, neutral potential (0 mv) colored gray, and negative potential (−20 mv) colored red. The binding pockets are labeled in yellow. The P1, P4, and P6 pockets appear acidic in contrast to the more basic P7 and P9 pockets.(B) The solvent-accessible surface ([13]) of the I-A^g7 peptide binding groove (blue) viewed from the side as a cross section. The HEL peptide is represented as a CPK model: carbon atoms, yellow; nitrogen atoms, blue; sulfur atoms, green; and oxygen atoms, red. In addition to the usual peptide anchor side chains (P1, P4, P6, P7, and P9), the P10 side chain also makes extensive contact with the I-A^g7 molecule. The HEL peptide buries 81% (334 Å^2) of its main chain and 72% (612 Å^2) of it side chain surface area.(C) Proposed alignment of I-A^g7 binding peptides. The upper panel lists eight different I-A^g7 binding peptides: G6PI (glucose-6-phosphate isomerase, 282–294) (P. M. Allen, personal communication); GAD65a (glutamic acid decarboxylase, 207–220) and GAD65b (glutamic acid decarboxylase, 222–235) ([10]); MSA (mouse serum albumin, 563–573); Tnf (transferrin, 57–68); Apo (apolipoprotein B, 100–113); Actin (actin, 73–85); and Insulin (Insulinβ, 10–23) ( [36]). The peptides were aligned based on a structural analysis of the shape and chemical nature of the binding groove. Shown in the lower panel is a set of single amino acid substitutions made at HEL(11–25) anchor positions. Listed beside each peptide sequence is an IC50 value, the concentration of peptide required to inhibit 50% of the binding of a reference peptide to I-A^g7. NB, no binding; ND, not determined.
Figure 5.
Figure 5. Binding of HEL(11–25) to Soluble I-A^g7(A) Schematic outline of the cDNA construct used to produce soluble I-A^g7 molecules. Chain pairing was encouraged by the addition of leucine zipper acid and base tails at the C termini ([9]). A peptide (from HEL or CLIP) was encoded at the N terminus of the β chain ( [27]). The soluble I-A^g7 protein was purified from baculovirus-infected insect cell supernatants and treated with thrombin to release the peptide and leucine zipper tails.(B) Representative curve for the binding of radiolabeled HEL(11–25) peptide to purified thrombin-cleaved I-A^g7. The inset panel contains a Scatchard analysis of this binding, which yielded an apparent KD of 6.0 μM. The binding of HEL(48–61) peptide to soluble thrombin-cleaved I-A^k performed under similar conditions yielded an apparent KD of 0.1 μM.
  The above figures are reprinted by permission from Cell Press: Immunity (2000, 12, 699-710) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23274471 H.von Boehmer, and C.Daniel (2012).
Therapeutic opportunities for manipulating T(Reg) cells in autoimmunity and cancer.
  Nat Rev Drug Discov, 12, 51-63.  
21505262 C.Viret, S.Leung-Theung-Long, L.Serre, C.Lamare, D.A.Vignali, B.Malissen, A.Carrier, and S.Guerder (2011).
Thymus-specific serine protease controls autoreactive CD4 T cell development and autoimmune diabetes in mice.
  J Clin Invest, 121, 1810-1821.  
20534455 B.D.Stadinski, L.Zhang, F.Crawford, P.Marrack, G.S.Eisenbarth, and J.W.Kappler (2010).
Diabetogenic T cells recognize insulin bound to IAg7 in an unexpected, weakly binding register.
  Proc Natl Acad Sci U S A, 107, 10978-10983.  
20139986 B.D.Stadinski, T.Delong, N.Reisdorph, R.Reisdorph, R.L.Powell, M.Armstrong, J.D.Piganelli, G.Barbour, B.Bradley, F.Crawford, P.Marrack, S.K.Mahata, J.W.Kappler, and K.Haskins (2010).
Chromogranin A is an autoantigen in type 1 diabetes.
  Nat Immunol, 11, 225-231.  
20093428 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, and T.P.Dilorenzo (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.
PDB codes: 3fol 3fom 3fon
20407212 K.Yoshida, A.L.Corper, R.Herro, B.Jabri, I.A.Wilson, and L.Teyton (2010).
The diabetogenic mouse MHC class II molecule I-Ag7 is endowed with a switch that modulates TCR affinity.
  J Clin Invest, 120, 1578-1590.
PDB code: 3mbe
19557406 E.Janova, J.Matiasovic, J.Vahala, R.Vodicka, E.Van Dyk, and P.Horin (2009).
Polymorphism and selection in the major histocompatibility complex DRA and DQA genes in the family Equidae.
  Immunogenetics, 61, 513-527.  
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.  
18055025 A.Suri, and A.Szallasi (2008).
The emerging role of TRPV1 in diabetes and obesity.
  Trends Pharmacol Sci, 29, 29-36.  
18082388 A.Suri, M.G.Levisetti, and E.R.Unanue (2008).
Do the peptide-binding properties of diabetogenic class II molecules explain autoreactivity?
  Curr Opin Immunol, 20, 105-110.  
18854049 C.S.Parry, and B.R.Brooks (2008).
A new model defines the minimal set of polymorphism in HLA-DQ and -DR that determines susceptibility and resistance to autoimmune diabetes.
  Biol Direct, 3, 42.  
18492786 L.Li, B.Wang, J.A.Frelinger, and R.Tisch (2008).
T-cell promiscuity in autoimmune diabetes.
  Diabetes, 57, 2099-2106.  
18398138 M.G.Levisetti, D.M.Lewis, A.Suri, and E.R.Unanue (2008).
Weak proinsulin peptide-major histocompatibility complexes are targeted in autoimmune diabetes in mice.
  Diabetes, 57, 1852-1860.  
18195074 R.Jain, D.M.Tartar, R.K.Gregg, R.D.Divekar, J.J.Bell, H.H.Lee, P.Yu, J.S.Ellis, C.M.Hoeman, C.L.Franklin, and H.Zaghouani (2008).
Innocuous IFNgamma induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production.
  J Exp Med, 205, 207-218.  
17497145 G.P.Bondinas, A.K.Moustakas, and G.K.Papadopoulos (2007).
The spectrum of HLA-DQ and HLA-DR alleles, 2006: a listing correlating sequence and structure with function.
  Immunogenetics, 59, 539-553.  
17211830 K.Y.Chang, A.Suri, and E.R.Unanue (2007).
Predicting peptides bound to I-Ag7 class II histocompatibility molecules using a novel expectation-maximization alignment algorithm.
  Proteomics, 7, 367-377.  
18031584 M.Rajapakse, B.Schmidt, L.Feng, and V.Brusic (2007).
Predicting peptides binding to MHC class II molecules using multi-objective evolutionary algorithms.
  BMC Bioinformatics, 8, 459.  
16316750 A.Suri, S.B.Lovitch, and E.R.Unanue (2006).
The wide diversity and complexity of peptides bound to class II MHC molecules.
  Curr Opin Immunol, 18, 70-77.  
16557259 E.Y.Jones, L.Fugger, J.L.Strominger, and C.Siebold (2006).
MHC class II proteins and disease: a structural perspective.
  Nat Rev Immunol, 6, 271-282.  
16467985 J.Bryja, M.Galan, N.Charbonnel, and J.F.Cosson (2006).
Duplication, balancing selection and trans-species evolution explain the high levels of polymorphism of the DQA MHC class II gene in voles (Arvicolinae).
  Immunogenetics, 58, 191-202.  
16075062 A.Suri, J.J.Walters, M.L.Gross, and E.R.Unanue (2005).
Natural peptides selected by diabetogenic DQ8 and murine I-A(g7) molecules show common sequence specificity.
  J Clin Invest, 115, 2268-2276.  
15826953 E.Bergseng, J.Xia, C.Y.Kim, C.Khosla, and L.M.Sollid (2005).
Main chain hydrogen bond interactions in the binding of proline-rich gluten peptides to the celiac disease-associated HLA-DQ2 molecule.
  J Biol Chem, 280, 21791-21796.  
15790362 R.Gianani, and G.S.Eisenbarth (2005).
The stages of type 1A diabetes: 2005.
  Immunol Rev, 204, 232-249.  
16181330 T.H.Hansen, L.Lybarger, L.Yu, V.Mitaksov, and D.H.Fremont (2005).
Recognition of open conformers of classical MHC by chaperones and monoclonal antibodies.
  Immunol Rev, 207, 100-111.  
14769912 C.Siebold, B.E.Hansen, J.R.Wyer, K.Harlos, R.E.Esnouf, A.Svejgaard, J.I.Bell, J.L.Strominger, E.Y.Jones, and L.Fugger (2004).
Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy.
  Proc Natl Acad Sci U S A, 101, 1999-2004.
PDB code: 1uvq
14744995 F.F.Shih, L.Mandik-Nayak, B.T.Wipke, and P.M.Allen (2004).
Massive thymic deletion results in systemic autoimmunity through elimination of CD4+ CD25+ T regulatory cells.
  J Exp Med, 199, 323-335.  
15517241 R.A.Ettinger, A.K.Moustakas, and S.D.Lobaton (2004).
Open reading frame sequencing and structure-based alignment of polypeptides encoded by RT1-Bb, RT1-Ba, RT1-Db, and RT1-Da alleles.
  Immunogenetics, 56, 585-596.  
15084275 Z.Pu, S.B.Lovitch, E.K.Bikoff, and E.R.Unanue (2004).
T cells distinguish MHC-peptide complexes formed in separate vesicles and edited by H2-DM.
  Immunity, 20, 467-476.  
12682304 A.Suri, J.J.Walters, O.Kanagawa, M.L.Gross, and E.R.Unanue (2003).
Specificity of peptide selection by antigen-presenting cells homozygous or heterozygous for expression of class II MHC molecules: The lack of competition.
  Proc Natl Acad Sci U S A, 100, 5330-5335.  
14679046 K.W.Wucherpfennig (2003).
MHC-linked susceptibility to type 1 diabetes: a structural perspective.
  Ann N Y Acad Sci, 1005, 119-127.  
  12727928 N.R.Martinez, P.Augstein, A.K.Moustakas, G.K.Papadopoulos, S.Gregori, L.Adorini, D.C.Jackson, and L.C.Harrison (2003).
Disabling an integral CTL epitope allows suppression of autoimmune diabetes by intranasal proinsulin peptide.
  J Clin Invest, 111, 1365-1371.  
  12975475 T.Stratmann, N.Martin-Orozco, V.Mallet-Designe, L.Poirot, D.McGavern, G.Losyev, C.M.Dobbs, M.B.Oldstone, K.Yoshida, H.Kikutani, D.Mathis, C.Benoist, K.Haskins, and L.Teyton (2003).
Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity.
  J Clin Invest, 112, 902-914.  
12939341 W.A.Macdonald, A.W.Purcell, N.A.Mifsud, L.K.Ely, D.S.Williams, L.Chang, J.J.Gorman, C.S.Clements, L.Kjer-Nielsen, D.M.Koelle, S.R.Burrows, B.D.Tait, R.Holdsworth, A.G.Brooks, G.O.Lovrecz, L.Lu, J.Rossjohn, and J.McCluskey (2003).
A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition.
  J Exp Med, 198, 679-691.
PDB codes: 1m6o 1n2r
12367556 A.M.Marleau, and B.Singh (2002).
Myeloid dendritic cells in non-obese diabetic mice have elevated costimulatory and T helper-1-inducing abilities.
  J Autoimmun, 19, 23-35.  
11857638 B.J.McFarland, and C.Beeson (2002).
Binding interactions between peptides and proteins of the class II major histocompatibility complex.
  Med Res Rev, 22, 168-203.  
12055186 C.Velazquez, I.Vidavsky, K.van der Drift, M.L.Gross, and E.R.Unanue (2002).
Chemical identification of a low abundance lysozyme peptide family bound to I-Ak histocompatibility molecules.
  J Biol Chem, 277, 42514-42522.  
11956295 D.H.Fremont, S.Dai, H.Chiang, F.Crawford, P.Marrack, and J.Kappler (2002).
Structural basis of cytochrome c presentation by IE(k).
  J Exp Med, 195, 1043-1052.
PDB codes: 1kt2 1ktd
12190925 E.R.Unanue (2002).
Perspective on antigen processing and presentation.
  Immunol Rev, 185, 86.  
11943852 F.S.Wong, A.K.Moustakas, L.Wen, G.K.Papadopoulos, and C.A.Janeway (2002).
Analysis of structure and function relationships of an autoantigenic peptide of insulin bound to H-2K(d) that stimulates CD8 T cells in insulin-dependent diabetes mellitus.
  Proc Natl Acad Sci U S A, 99, 5551-5556.
PDB code: 1l6q
12413526 M.S.Anderson (2002).
Autoimmune endocrine disease.
  Curr Opin Immunol, 14, 760-764.  
12150894 X.L.He, C.Radu, J.Sidney, A.Sette, E.S.Ward, and K.C.Garcia (2002).
Structural snapshot of aberrant antigen presentation linked to autoimmunity: the immunodominant epitope of MBP complexed with I-Au.
  Immunity, 17, 83-94.
PDB code: 1k2d
12084926 X.Liu, S.Dai, F.Crawford, R.Fruge, P.Marrack, and J.Kappler (2002).
Alternate interactions define the binding of peptides to the MHC molecule IA(b).
  Proc Natl Acad Sci U S A, 99, 8820-8825.
PDB code: 1lnu
12084929 Z.Pu, J.A.Carrero, and E.R.Unanue (2002).
Distinct recognition by two subsets of T cells of an MHC class II-peptide complex.
  Proc Natl Acad Sci U S A, 99, 8844-8849.  
11712856 F.J.Quintana, and I.R.Cohen (2001).
Autoantibody patterns in diabetes-prone NOD mice and in standard C57BL/6 mice.
  J Autoimmun, 17, 191-197.  
11677085 K.W.Wucherpfennig (2001).
Insights into autoimmunity gained from structural analysis of MHC-peptide complexes.
  Curr Opin Immunol, 13, 650-656.  
11602644 T.P.Cirrito, Z.Pu, M.B.Deck, and E.R.Unanue (2001).
Deamidation of asparagine in a major histocompatibility complex-bound peptide affects T cell recognition but does not explain type B reactivity.
  J Exp Med, 194, 1165-1170.  
11106373 C.P.Liu, K.Jiang, C.H.Wu, W.H.Lee, and W.J.Lin (2000).
Detection of glutamic acid decarboxylase-activated T cells with I-Ag7 tetramers.
  Proc Natl Acad Sci U S A, 97, 14596-14601.  
11016975 R.R.Latek, S.J.Petzold, and E.R.Unanue (2000).
Hindering auxiliary anchors are potent modulators of peptide binding and selection by I-Ak class II molecules.
  Proc Natl Acad Sci U S A, 97, 11460-11465.  
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.