spacer
spacer

PDBsum entry 1ce6
Go to PDB code: 
protein ligands Protein-protein interface(s) links
Mhc class i PDB id
1ce6

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
274 a.a. *
99 a.a. *
Ligands
PHE-ALA-PRO-GLY-
ASN-TYR-PRO-ALA-
LEU
SO4
Waters ×25
* Residue conservation analysis
PDB id:
1ce6
Name: Mhc class i
Title: Mhc class i h-2db complexed with a sendai virus nucleoprotein peptide
Structure: Protein (mhc class i h-2db heavy chain). Chain: a. Fragment: fragment: extracellular domains. Engineered: yes. Protein (human beta-2 microglobulin). Chain: b. Engineered: yes. Protein (sendai virus nucleoprotein). Chain: c.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell: cho k1 cells. Homo sapiens. Human. Organism_taxid: 9606.
Biol. unit: Monomer (from PDB file)
Resolution:
2.90Å     R-factor:   0.217     R-free:   0.274
Authors: J.Tormo,E.Y.Jones
Key ref:
A.Glithero et al. (1999). Crystal structures of two H-2Db/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity. Immunity, 10, 63-74. PubMed id: 10023771 DOI: 10.1016/S1074-7613(00)80007-2
Date:
17-Mar-99     Release date:   26-Mar-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01899  (HA11_MOUSE) -  H-2 class I histocompatibility antigen, D-B alpha chain from Mus musculus
Seq:
Struc: 		362 a.a.
274 a.a.
Protein chain
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens
Seq:
Struc: 		119 a.a.
99 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/S1074-7613(00)80007-2 Immunity 10:63-74 (1999)
PubMed id: 10023771  
 
 
Crystal structures of two H-2Db/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity.
A.Glithero, J.Tormo, J.S.Haurum, G.Arsequell, G.Valencia, J.Edwards, S.Springer, A.Townsend, Y.L.Pao, M.Wormald, R.A.Dwek, E.Y.Jones, T.Elliott.
 
  ABSTRACT  
 
Two synthetic O-GlcNAc-bearing peptides that elicit H-2Db-restricted glycopeptide-specific cytotoxic T cells (CTL) have been shown to display nonreciprocal patterns of cross-reactivity. Here, we present the crystal structures of the H-2Db glycopeptide complexes to 2.85 A resolution or better. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex formed between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-MHC geometry. The models also reveal a possible molecular basis for the observed cross-reactivity patterns of the CTL clones, which appear to be influenced by the length of the CDR3 loop and the nature of the immunizing ligand.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Peptide StructuresThe peptides used in this study are based on an H-2D^b restricted CTL epitope (WT) from Sendai Virus nucleoprotein residues 324–332. K3G and K2G carry the Ser-O-GlcNAc substitution at positions 4 and 5 on the peptide backbone, respectively. The anchor residues for peptide binding to H-2D^b are underlined. 		Figure 6.
Figure 6. Anti-K2G CTL Are More Promiscuous than Anti-K3G CTLPeptide specificity of CTL clones K2G.6.9 (raised against K2G) and K3G.6.15 (raised against K3G) tested against ^51Cr-labeled target cells T2-D^b in the presence of K3G (upside down triangle), K2G (closed circle), K3G with a tyrosine to alanine substitution at position 6 (closed square), K3G with a proline to alanine substitution at position 7 (open diamond), and K3G with a lysine to alanine substitution at position 9 (closed triangle).
 
  The above figures are reprinted by permission from Cell Press: Immunity (1999, 10, 63-74) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference Google scholar

  PubMed id Reference
20617150 A.Pashov, B.Monzavi-Karbassi, G.P.Raghava, and T.Kieber-Emmons (2010).
Bridging innate and adaptive antitumor immunity targeting glycans.
  J Biomed Biotechnol, 2010, 354068.  
20635898 R.E.Beatson, J.Taylor-Papadimitriou, and J.M.Burchell (2010).
MUC1 immunotherapy.
  Immunotherapy, 2, 305-327.  
19544521 A.Fernández-Tejada, F.Corzana, J.H.Busto, G.Jiménez-Osés, J.Jiménez-Barbero, A.Avenoza, and J.M.Peregrina (2009).
Insights into the geometrical features underlying beta-O-GlcNAc glycosylation: water pockets drastically modulate the interactions between the carbohydrate and the peptide backbone.
  Chemistry, 15, 7297-7301.  
19363676 D.Hoja-Łukowicz, M.Przybyło, E.Pocheć, A.Drabik, J.Silberring, M.Kremser, D.Schadendorf, P.Laidler, and A.Lityńska (2009).
The new face of nucleolin in human melanoma.
  Cancer Immunol Immunother, 58, 1471-1480.  
19007994 T.Ninkovic, L.Kinarsky, K.Engelmann, V.Pisarev, S.Sherman, O.J.Finn, and F.G.Hanisch (2009).
Identification of O-glycosylated decapeptides within the MUC1 repeat domain as potential MHC class I (A2) binding epitopes.
  Mol Immunol, 47, 131-140.  
18245382 G.M.Grotenbreg, N.R.Roan, E.Guillen, R.Meijers, J.H.Wang, G.W.Bell, M.N.Starnbach, and H.L.Ploegh (2008).
Discovery of CD8+ T cell epitopes in Chlamydia trachomatis infection through use of caged class I MHC tetramers.
  Proc Natl Acad Sci U S A, 105, 3831-3836.
PDB code: 2ve6
16478731 A.Glithero, J.Tormo, K.Doering, M.Kojima, E.Y.Jones, and T.Elliott (2006).
The crystal structure of H-2D(b) complexed with a partial peptide epitope suggests a major histocompatibility complex class I assembly intermediate.
  J Biol Chem, 281, 12699-12704.
PDB code: 2cii
16297661 S.R.Burrows, J.Rossjohn, and J.McCluskey (2006).
Have we cut ourselves too short in mapping CTL epitopes?
  Trends Immunol, 27, 11-16.  
16473882 V.Mitaksov, and D.H.Fremont (2006).
Structural definition of the H-2Kd peptide-binding motif.
  J Biol Chem, 281, 10618-10625.
PDB code: 2fwo
15771591 E.S.Trombetta, and I.Mellman (2005).
Cell biology of antigen processing in vitro and in vivo.
  Annu Rev Immunol, 23, 975.  
15849183 F.E.Tynan, N.A.Borg, J.J.Miles, T.Beddoe, D.El-Hassen, S.L.Silins, W.J.van Zuylen, A.W.Purcell, L.Kjer-Nielsen, J.McCluskey, S.R.Burrows, and J.Rossjohn (2005).
High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I. Implications for T-cell receptor engagement and T-cell immunodominance.
  J Biol Chem, 280, 23900-23909.
PDB codes: 1zhk 1zhl
16069816 M.M.Fuster, and J.D.Esko (2005).
The sweet and sour of cancer: glycans as novel therapeutic targets.
  Nat Rev Cancer, 5, 526-542.  
16181329 T.Elliott, and A.Williams (2005).
The optimization of peptide cargo bound to MHC class I molecules by the peptide-loading complex.
  Immunol Rev, 207, 89-99.  
15056041 V.Apostolopoulos, and E.Lazoura (2004).
Noncanonical peptides in complex with MHC class I.
  Expert Rev Vaccines, 3, 151-162.  
12558945 J.Schuman, A.P.Campbell, R.R.Koganty, and B.M.Longenecker (2003).
Probing the conformational and dynamical effects of O-glycosylation within the immunodominant region of a MUC1 peptide tumor antigen.
  J Pept Res, 61, 91.  
14657390 V.Apostolopoulos, E.Yuriev, P.A.Ramsland, J.Halton, C.Osinski, W.Li, M.Plebanski, H.Paulsen, and I.F.McKenzie (2003).
A glycopeptide in complex with MHC class I uses the GalNAc residue as an anchor.
  Proc Natl Acad Sci U S A, 100, 15029-15034.  
12479822 A.Achour, J.Michaëlsson, R.A.Harris, J.Odeberg, P.Grufman, J.K.Sandberg, V.Levitsky, K.Kärre, T.Sandalova, and G.Schneider (2002).
A structural basis for LCMV immune evasion: subversion of H-2D(b) and H-2K(b) presentation of gp33 revealed by comparative crystal structure.Analyses.
  Immunity, 17, 757-768.
PDB codes: 1n59 1n5a
12461079 A.M.Vlad, S.Muller, M.Cudic, H.Paulsen, L.Otvos, F.G.Hanisch, and O.J.Finn (2002).
Complex carbohydrates are not removed during processing of glycoproteins by dendritic cells: processing of tumor antigen MUC1 glycopeptides for presentation to major histocompatibility complex class II-restricted T cells.
  J Exp Med, 196, 1435-1446.  
11943376 B.Monzavi-Karbassi, G.Cunto-Amesty, P.Luo, and T.Kieber-Emmons (2002).
Peptide mimotopes as surrogate antigens of carbohydrates in vaccine discovery.
  Trends Biotechnol, 20, 207-214.  
12470741 K.Vosseller, K.Sakabe, L.Wells, and G.W.Hart (2002).
Diverse regulation of protein function by O-GlcNAc: a nuclear and cytoplasmic carbohydrate post-translational modification.
  Curr Opin Chem Biol, 6, 851-857.  
11926165 L.C.Heukamp, T.van Hall, F.Ossendorp, J.M.Burchell, C.J.Melief, J.Taylor-Papadimitriou, and R.Offringa (2002).
Effective immunotherapy of cancer in MUC1-transgenic mice using clonal cytotoxic T lymphocytes directed against an immunodominant MUC1 epitope.
  J Immunother (1997), 25, 46-56.  
11790533 M.G.Rudolph, and I.A.Wilson (2002).
The specificity of TCR/pMHC interaction.
  Curr Opin Immunol, 14, 52-65.  
12122209 O.Werdelin, M.Meldal, and T.Jensen (2002).
Processing of glycans on glycoprotein and glycopeptide antigens in antigen-presenting cells.
  Proc Natl Acad Sci U S A, 99, 9611-9613.  
12010576 P.E.Adrian, G.Rajaseger, V.S.Mathura, M.K.Sakharkar, and P.Kangueane (2002).
Types of inter-atomic interactions at the MHC-peptide interface: identifying commonality from accumulated data.
  BMC Struct Biol, 2, 2.  
11536167 F.Housseau, A.Moorthy, D.A.Langer, P.F.Robbins, M.I.Gonzales, and S.L.Topalian (2001).
N-linked carbohydrates in tyrosinase are required for its recognition by human MHC class II-restricted CD4(+) T cells.
  Eur J Immunol, 31, 2690-2701.  
11473834 H.A.Doyle, and M.J.Mamula (2001).
Post-translational protein modifications in antigen recognition and autoimmunity.
  Trends Immunol, 22, 443-449.  
11269318 P.M.Rudd, T.Elliott, P.Cresswell, I.A.Wilson, and R.A.Dwek (2001).
Glycosylation and the immune system.
  Science, 291, 2370-2376.  
11158680 T.I.Prigozy, O.Naidenko, P.Qasba, D.Elewaut, L.Brossay, A.Khurana, T.Natori, Y.Koezuka, A.Kulkarni, and M.Kronenberg (2001).
Glycolipid antigen processing for presentation by CD1d molecules.
  Science, 291, 664-667.  
10981968 A.Shamshiev, A.Donda, T.I.Prigozy, L.Mori, V.Chigorno, C.A.Benedict, L.Kappos, S.Sonnino, M.Kronenberg, and G.De Libero (2000).
The alphabeta T cell response to self-glycolipids shows a novel mechanism of CD1b loading and a requirement for complex oligosaccharides.
  Immunity, 13, 255-264.  
11053110 A.Simon, Z.Dosztányi, E.Rajnavölgyi, and I.Simon (2000).
Function-related regulation of the stability of MHC proteins.
  Biophys J, 79, 2305-2313.  
10634787 C.Wingren, M.P.Crowley, M.Degano, Y.Chien, and I.A.Wilson (2000).
Crystal structure of a gammadelta T cell receptor ligand T22: a truncated MHC-like fold.
  Science, 287, 310-314.
PDB code: 1c16
  11152131 J.Yagüe, J.Vázquez, and J.A.López de Castro (2000).
A post-translational modification of nuclear proteins, N(G),N(G)-dimethyl-Arg, found in a natural HLA class I peptide ligand.
  Protein Sci, 9, 2210-2217.  
  11045629 O.Schueler-Furman, Y.Altuvia, A.Sette, and H.Margalit (2000).
Structure-based prediction of binding peptides to MHC class I molecules: application to a broad range of MHC alleles.
  Protein Sci, 9, 1838-1846.  
11828414 O.Seitz (2000).
Glycopeptide synthesis and the effects of glycosylation on protein structure and activity.
  Chembiochem, 1, 214-246.  
10631954 D.B.Moody, G.S.Besra, I.A.Wilson, and S.A.Porcelli (1999).
The molecular basis of CD1-mediated presentation of lipid antigens.
  Immunol Rev, 172, 285-296.  
10593916 D.Hudrisier, J.Riond, H.Mazarguil, M.B.Oldstone, and J.E.Gairin (1999).
Genetically encoded and post-translationally modified forms of a major histocompatibility complex class I-restricted antigen bearing a glycosylation motif are independently processed and co-presented to cytotoxic T lymphocytes.
  J Biol Chem, 274, 36274-36280.  
10429679 J.S.Haurum, I.B.Høier, G.Arsequell, A.Neisig, G.Valencia, J.Zeuthen, J.Neefjes, and T.Elliott (1999).
Presentation of cytosolic glycosylated peptides by human class I major histocompatibility complex molecules in vivo.
  J Exp Med, 190, 145-150.  
10607669 K.Maenaka, and E.Y.Jones (1999).
MHC superfamily structure and the immune system.
  Curr Opin Struct Biol, 9, 745-753.  
10508250 T.Jensen, P.Hansen, A.Faurskov Nielsen, M.Meldal, S.Komba, and O.Werdelin (1999).
Shared structural motifs in TCR of glycopeptide-recognizing T cell hybridomas.
  Eur J Immunol, 29, 2759-2768.  
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.

 

spacer
spacer