PDBsum entry 1k2d

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Immune system PDB id
Protein chains
182 a.a. *
185 a.a. *
12 a.a. *
NAG ×2
Waters ×450
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structure of the autoimmune mhc class ii i-au comple myelin basic protein 1-11 at 2.2a
Structure: H-2 class ii histocompatibility antigen, a-u alph chain: a. Fragment: extracellular alpha-1 and alpha-2 domains. Synonym: mhc class ii i-au. Engineered: yes. H-2 class ii histocompatibility antigen, a-u beta chain: b. Fragment: extracellular beta-1 and beta-2 domains. Synonym: mhc class ii i-au.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Synthetic: yes. Other_details: the peptide was chemically synthesized. The of the mbp portion of the peptide is naturally found in hom (human).
Biol. unit: Trimer (from PQS)
2.20Å     R-factor:   0.248     R-free:   0.276
Authors: X.L.He,C.Radu,E.S.Ward,K.C.Garcia
Key ref:
X.L.He et al. (2002). Structural snapshot of aberrant antigen presentation linked to autoimmunity: the immunodominant epitope of MBP complexed with I-Au. Immunity, 17, 83-94. PubMed id: 12150894 DOI: 10.1016/S1074-7613(02)00340-0
26-Sep-01     Release date:   04-Mar-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P14438  (HA2U_MOUSE) -  H-2 class II histocompatibility antigen, A-U alpha chain (Fragment)
227 a.a.
182 a.a.
Protein chain
Pfam   ArchSchema ?
P06344  (HB2U_MOUSE) -  H-2 class II histocompatibility antigen, A-U beta chain
263 a.a.
185 a.a.
Protein chain
Pfam   ArchSchema ?
P02686  (MBP_HUMAN) -  Myelin basic protein
304 a.a.
12 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

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


DOI no: 10.1016/S1074-7613(02)00340-0 Immunity 17:83-94 (2002)
PubMed id: 12150894  
Structural snapshot of aberrant antigen presentation linked to autoimmunity: the immunodominant epitope of MBP complexed with I-Au.
X.L.He, C.Radu, J.Sidney, A.Sette, E.S.Ward, K.C.Garcia.
Murine experimental allergic encephalomyelitis (EAE) is a useful model for the demyelinating, autoimmune disease multiple sclerosis. In the EAE system, the immunodominant N-terminal epitope of myelin basic protein (MBP) is an unusually short, weakly binding peptide antigen which elicits highly biased TCR chain usage. In the 2.2 A crystal structure of I-A(u)/MBP1-11 complex, only MBP residues 1-7 are bound toward one end of the peptide binding cleft. The fourth residue of MBP1-11 is located in an incompatible p6 pocket of I-A(u), thus explaining the short half-life of I-A(u) complexed with Ac1-11. MBP peptides extended at the C terminus of Ac1-11 result in dramatic affinity increases, likely attributed to register shifting to a higher affinity cryptic epitope, which could potentially mask the presentation of the immunodominant MBP1-11 peptide during thymic education.
  Selected figure(s)  
Figure 2.
Figure 2. Molecular Surface Complementarity between the I-A^u Groove and the MBP PeptideTo depict the natural Ac-11 peptide, the residual leader peptide residues have been removed from the structure. Molecular surfaces of I-A^u (blue) with bound MBP peptide (purple) were produced, and the figures show planar cross sections through these surfaces to illustrate the shape and complementarity between peptide and MHC, as well as unfilled pockets and ordered water molecules (red spheres). The MBP peptide is shown within the surface as silver sticks. (A) is a side view, as in Figure 1C, and (B) is the groove viewed from the top, as in Figure 1D. Due to the planar cross section of the convoluted surfaces, some residues of the peptide are sliced out of view, such as P5-Arg, which extends toward the reader in (A) and (B). In (A), the large and spacious p6 pocket is apparent, as are the ordered water molecules in the p1 and p6 pockets. In (B), the empty p1 pocket is in the far left of the blue I-A^u molecular surface, and the p7 pocket, where the P5-Arg resides, extends sideways but does not appear occupied by P5-Arg due to the cross section. The molecular surfaces were produced using a 1.4 Å probe radius.
Figure 3.
Figure 3. MBP Peptide Interactions with I-A^uThe orientation is as for the side view shown in Figure 1, with the peptide (purple) N terminus to the left and C terminus to the right. I-A^u β chain helix is in front (gray tube), and α chain helix is in back (gray) of the peptide. The residues of I-A^u which interact with the peptide are drawn as cyan. H bonds are indicated as green dots. Relevant residues are labeled for the (A) N-terminal, (B) central, and (C) more C-terminal MBP peptide interactions with I-A^u.
  The above figures are reprinted by permission from Cell Press: Immunity (2002, 17, 83-94) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21199956 D.K.Sethi, D.A.Schubert, A.K.Anders, A.Heroux, D.A.Bonsor, C.P.Thomas, E.J.Sundberg, J.Pyrdol, and K.W.Wucherpfennig (2011).
A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC.
  J Exp Med, 208, 91.
PDB code: 3pl6
21488900 J.M.Goverman (2011).
Immune tolerance in multiple sclerosis.
  Immunol Rev, 241, 228-240.  
21306912 K.W.Wucherpfennig, and D.Sethi (2011).
T cell receptor recognition of self and foreign antigens in the induction of autoimmunity.
  Semin Immunol, 23, 84-91.  
21297580 Y.Yin, Y.Li, M.C.Kerzic, R.Martin, and R.A.Mariuzza (2011).
Structure of a TCR with high affinity for self-antigen reveals basis for escape from negative selection.
  EMBO J, 30, 1137-1148.
PDB code: 3o6f
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.  
20657836 B.Knapp, U.Omasits, W.Schreiner, and M.M.Epstein (2010).
A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.
  PLoS One, 5, e11653.  
20412755 B.Stadinski, J.Kappler, and G.S.Eisenbarth (2010).
Molecular targeting of islet autoantigens.
  Immunity, 32, 446-456.  
20306469 V.Cecconi, M.Moro, S.Del Mare, J.Sidney, A.Bachi, R.Longhi, A.Sette, M.P.Protti, P.Dellabona, and G.Casorati (2010).
The CD4+ T-cell epitope-binding register is a critical parameter when generating functional HLA-DR tetramers with promiscuous peptides.
  Eur J Immunol, 40, 1603-1616.  
19063692 D.Kanduc (2009).
Epitopic peptides with low similarity to the host proteome: towards biological therapies without side effects.
  Expert Opin Biol Ther, 9, 45-53.  
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.  
  19359524 R.Arakaki, A.Nagaoka, N.Ishimaru, A.Yamada, S.Yoshida, and Y.Hayashi (2009).
Role of plasmacytoid dendritic cells for aberrant class II expression in exocrine glands from estrogen-deficient mice of healthy background.
  Am J Pathol, 174, 1715-1724.  
20224179 Y.Hayashi, R.Arakaki, and N.Ishimaru (2009).
Salivary gland and autoimmunity.
  J Med Invest, 56, 185-191.  
18155234 C.McBeth, A.Seamons, J.C.Pizarro, S.J.Fleishman, D.Baker, T.Kortemme, J.M.Goverman, and R.K.Strong (2008).
A new twist in TCR diversity revealed by a forbidden alphabeta TCR.
  J Mol Biol, 375, 1306-1319.
PDB codes: 2p1y 2p24
19015307 N.Ishimaru, R.Arakaki, S.Yoshida, A.Yamada, S.Noji, and Y.Hayashi (2008).
Expression of the retinoblastoma protein RbAp48 in exocrine glands leads to Sjögren's syndrome-like autoimmune exocrinopathy.
  J Exp Med, 205, 2915-2927.  
  19017944 W.Mi, S.Wanjie, S.T.Lo, Z.Gan, B.Pickl-Herk, R.J.Ober, and E.S.Ward (2008).
Targeting the neonatal fc receptor for antigen delivery using engineered fc fragments.
  J Immunol, 181, 7550-7561.  
17694060 D.Feng, C.J.Bond, L.K.Ely, J.Maynard, and K.C.Garcia (2007).
Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'.
  Nat Immunol, 8, 975-983.
PDB codes: 2pxy 2z31 2z35
17560120 E.J.Sundberg, L.Deng, and R.A.Mariuzza (2007).
TCR recognition of peptide/MHC class II complexes and superantigens.
  Semin Immunol, 19, 262-271.  
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.  
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.  
17848196 S.Glatigny, M.A.Blaton, J.Marin, S.Mistou, J.P.Briand, G.Guichard, C.Fournier, and G.Chiocchia (2007).
Insights into spatial configuration of a galactosylated epitope required to trigger arthritogenic T-cell receptors specific for the sugar moiety.
  Arthritis Res Ther, 9, R92.  
16453383 A.Ben-Nun, N.Kerlero de Rosbo, N.Kaushansky, M.Eisenstein, L.Cohen, J.F.Kaye, and I.Mendel (2006).
Anatomy of T cell autoimmunity to myelin oligodendrocyte glycoprotein (MOG): prime role of MOG44F in selection and control of MOG-reactive T cells in H-2b mice.
  Eur J Immunol, 36, 478-493.  
16361316 F.C.Kurschus, T.Oelert, B.Liliensiek, P.Buchmann, D.C.Wraith, G.J.Hämmerling, and B.Arnold (2006).
Experimental autoimmune encephalomyelitis in mice expressing the autoantigen MBP 1-10 covalently bound to the MHC class II molecule I-Au.
  Int Immunol, 18, 151-162.  
16551255 M.G.Rudolph, R.L.Stanfield, and I.A.Wilson (2006).
How TCRs bind MHCs, peptides, and coreceptors.
  Annu Rev Immunol, 24, 419-466.  
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.  
15664161 J.Maynard, K.Petersson, D.H.Wilson, E.J.Adams, S.E.Blondelle, M.J.Boulanger, D.B.Wilson, and K.C.Garcia (2005).
Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity.
  Immunity, 22, 81-92.
PDB code: 1u3h
16007090 M.Koch, V.S.Stronge, D.Shepherd, S.D.Gadola, B.Mathew, G.Ritter, A.R.Fersht, G.S.Besra, R.R.Schmidt, E.Y.Jones, and V.Cerundolo (2005).
The crystal structure of human CD1d with and without alpha-galactosylceramide.
  Nat Immunol, 6, 819-826.
PDB code: 1zt4
16181344 S.B.Lovitch, and E.R.Unanue (2005).
Conformational isomers of a peptide-class II major histocompatibility complex.
  Immunol Rev, 207, 293-313.  
16079912 Y.Li, Y.Huang, J.Lue, J.A.Quandt, R.Martin, and R.A.Mariuzza (2005).
Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule.
  EMBO J, 24, 2968-2979.
PDB code: 1zgl
15291817 A.G.Tzakos, P.Fuchs, N.A.van Nuland, A.Troganis, T.Tselios, S.Deraos, J.Matsoukas, I.P.Gerothanassis, and A.M.Bonvin (2004).
NMR and molecular dynamics studies of an autoimmune myelin basic protein peptide and its antagonist: structural implications for the MHC II (I-Au)-peptide complex from docking calculations.
  Eur J Biochem, 271, 3399-3413.  
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.  
12756272 A.Seamons, J.Sutton, D.Bai, E.Baird, N.Bonn, B.F.Kafsack, J.Shabanowitz, D.F.Hunt, C.Beeson, and J.Goverman (2003).
Competition between two MHC binding registers in a single peptide processed from myelin basic protein influences tolerance and susceptibility to autoimmunity.
  J Exp Med, 197, 1391-1397.  
12707414 E.Maverakis, J.Beech, D.B.Stevens, A.Ametani, L.Brossay, P.van den Elzen, R.Mendoza, Q.Thai, L.H.Macias, D.Ethell, C.W.Campagnoni, A.T.Campagnoni, A.Sette, and E.E.Sercarz (2003).
Autoreactive T cells can be protected from tolerance induction through competition by flanking determinants for access to class II MHC.
  Proc Natl Acad Sci U S A, 100, 5342-5347.  
12773544 R.H.McMahan, L.Watson, R.Meza-Romero, G.G.Burrows, D.N.Bourdette, and A.C.Buenafe (2003).
Production, characterization, and immunogenicity of a soluble rat single chain T cell receptor specific for an encephalitogenic peptide.
  J Biol Chem, 278, 30961-30970.  
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.