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PDBsum entry 1lnu

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protein ligands Protein-protein interface(s) links
Sugar binding protein PDB id
1lnu
Jmol
Contents
Protein chains
182 a.a. *
217 a.a. *
Ligands
NAG ×11
NDG
Waters ×237
* Residue conservation analysis
PDB id:
1lnu
Name: Sugar binding protein
Title: Crystal structure of class ii mhc molecule iab bound to ealp peptide
Structure: H-2 class ii histocompatibility antigen, a-b alph chain: a, c, e, g. Synonym: iaalpha. Engineered: yes. H-2 class ii histocompatibility antigen, a beta c chain: b, d, f, h. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
2.50Å     R-factor:   0.211     R-free:   0.245
Authors: X.Liu,S.Dai,F.Crawford,R.Fruge,P.Marrack,J.Kappler
Key ref:
X.Liu et al. (2002). Alternate interactions define the binding of peptides to the MHC molecule IA(b). Proc Natl Acad Sci U S A, 99, 8820-8825. PubMed id: 12084926 DOI: 10.1073/pnas.132272099
Date:
03-May-02     Release date:   14-Aug-02    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P14434  (HA2B_MOUSE) -  H-2 class II histocompatibility antigen, A-B alpha chain
Seq:
Struc:
256 a.a.
182 a.a.
Protein chains
Pfam   ArchSchema ?
P14483  (HB2A_MOUSE) -  H-2 class II histocompatibility antigen, A beta chain
Seq:
Struc:
265 a.a.
217 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 24 residue positions (black crosses)

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

 

 
DOI no: 10.1073/pnas.132272099 Proc Natl Acad Sci U S A 99:8820-8825 (2002)
PubMed id: 12084926  
 
 
Alternate interactions define the binding of peptides to the MHC molecule IA(b).
X.Liu, S.Dai, F.Crawford, R.Fruge, P.Marrack, J.Kappler.
 
  ABSTRACT  
 
We have solved the crystal structure of the MHCII molecule, IA(b), containing an antigenic variant of the major IA(b)-binding peptide derived from the MHCII IEalpha chain. The four MHC pockets at p1, p4, p6, and p9 that usually bind peptide side chains are largely empty because of alanines in the peptide at these positions. The complex is nevertheless very stable, apparently because of unique alternate interactions between the IA(b) and peptide. In particular, there are multiple additional hydrogen bonds between the N-terminal end of the peptide and the IA(b) alpha chain and an extensive hydrogen bond network involving an asparagine at p7 position of the peptide and the IA(b) beta chain. By using knowledge of the shape and size of the traditional side chain binding pockets and the additional possible interactions, an IA(b) peptide-binding motif can be deduced that agrees well with the sequences of known IA(b)-binding peptides.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Extensive interaction of p3K with IA^b. (A) The footprint of p3K on the solvent-accessible surface of the IA^b molecule. The surface has been colored to reflect the distance of the peptide from the IA^b surface: magenta, closest; white, intermediate; gray, farthest. Figure was created with PROTEIN EXPLORER (54). (B) Details of the predicted H-bond interactions (green dotted lines) between p-2Phe and p-1Glu of p3K and the IA^b chain are shown. (C) Details of the predicted H-bond interactions (green dotted lines) between p7Asn and the IA^b chain are shown. Two water molecules (W) involved in the interactions are shown (cyan). View is from the C-terminal end of the peptide toward its N terminus. In B and C (produced with SWISS PDB VIEWER) underlined amino acids differ between IA^b and IA^d.
Figure 4.
Fig. 4. The IA^b peptide binding motif. Sixty-four peptides found bound to IA^b (48) were aligned by attempting to place an aliphatic/aromatic amino acid at p1 and amino acids with small aliphatic or neutral side chains at p4, p6, and p9. If more than one alignment was possible, secondary consideration was given to the placement of a Glu or Gln at p-1 and/or an Asn, Asp, Glu, or Gln at p6. (A) Alignment of 13 representative peptides showing the portion of the peptide from p-2 to p11 aligned to p3K. Self peptides (48): pE = amino acids 54-66 of IE chain; CLP36 = amino acids 140-152 of CLP-36; ApoB = amino acids 769-781 of apolipoprotein B; GAPDH = amino acids 228-242 of glyceraldehyde-3-phosphate dehydrogenase; DEC205 = amino acids 567-579 of DEC205 receptor; CTLA4 = amino acids 38-50 of CTLA-4; H2DM = amino acids 140-152 of H-2DM chain; INT 1 = amino acids 781-793 of integrin -1; CD98 = amino acids 210-222 of CD98 heavy chain; CLIP = amino acids 88-100 of invariant chain. Foreign peptides: OVA = aa 327-338 of chicken ovalbumin (42); pE (2W) = pE (Q57W,I63W) (25, 39); PCC = aa 43-55 of pigeon cytochrome c (47, 50). (B) Summary of the alignment of all self peptides. The frequency (%) of the five most frequent amino acids at each position from p-1 to p9 is shown. Bar is the frequency of the most frequent amino acid. Open bars, p1, p4, p6, and p9 anchors; gray bars, other MHC-interacting amino acids; solid bars, potential T cell-interacting amino acids.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20421471 C.C.Govern, M.K.Paczosa, A.K.Chakraborty, and E.S.Huseby (2010).
Fast on-rates allow short dwell time ligands to activate T cells.
  Proc Natl Acad Sci U S A, 107, 8724-8729.  
20373997 J.L.Nayak, K.A.Richards, F.A.Chaves, and A.J.Sant (2010).
Analyses of the specificity of CD4 T cells during the primary immune response to influenza virus reveals dramatic MHC-linked asymmetries in reactivity to individual viral proteins.
  Viral Immunol, 23, 169-180.  
20026741 T.M.Johanns, J.M.Ertelt, J.C.Lai, J.H.Rowe, R.A.Avant, and S.S.Way (2010).
Naturally occurring altered peptide ligands control Salmonella-specific CD4+ T cell proliferation, IFN-gamma production, and protective potency.
  J Immunol, 184, 869-876.  
19443805 S.Subramanian, B.Zhang, Y.Kosaka, G.G.Burrows, M.R.Grafe, A.A.Vandenbark, P.D.Hurn, and H.Offner (2009).
Recombinant T cell receptor ligand treats experimental stroke.
  Stroke, 40, 2539-2545.  
17920446 E.S.Huseby, J.W.Kappler, and P.Marrack (2008).
Thymic selection stifles TCR reactivity with the main chain structure of MHC and forces interactions with the peptide side chains.
  Mol Immunol, 45, 599-606.  
  18453626 N.K.Brown, D.J.McCormick, C.S.David, and Y.C.Kong (2008).
H2E-derived Ealpha52-68 peptide presented by H2Ab interferes with clonal deletion of autoreactive T cells in autoimmune thyroiditis.
  J Immunol, 180, 7039-7046.  
18308592 S.Dai, E.S.Huseby, K.Rubtsova, J.Scott-Browne, F.Crawford, W.A.Macdonald, P.Marrack, and J.W.Kappler (2008).
Crossreactive T Cells spotlight the germline rules for alphabeta T cell-receptor interactions with MHC molecules.
  Immunity, 28, 324-334.
PDB codes: 3c5z 3c60 3c6l
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.  
17560121 K.Choudhuri, and P.A.van der Merwe (2007).
Molecular mechanisms involved in T cell receptor triggering.
  Semin Immunol, 19, 255-261.  
17549734 N.Kaushansky, R.Hemo, M.Eisenstein, and A.Ben-Nun (2007).
OSP/claudin-11-induced EAE in mice is mediated by pathogenic T cells primarily governed by OSP192Y residue of major encephalitogenic region OSP179-207.
  Eur J Immunol, 37, 2018-2031.  
17935073 N.Kaushansky, R.Zilkha-Falb, R.Hemo, H.Lassman, M.Eisenstein, A.Sas, and A.Ben-Nun (2007).
Pathogenic T cells in MOBP-induced murine EAE are predominantly focused to recognition of MOBP21F and MOBP27P epitopic residues.
  Eur J Immunol, 37, 3281-3292.  
17386582 S.Li, X.Yao, H.Liu, J.Li, and B.Fan (2007).
Prediction of T-cell epitopes based on least squares support vector machines and amino acid properties.
  Anal Chim Acta, 584, 37-42.  
17444955 W.Brintnell, D.A.Bell, J.A.Hill, A.M.Jevnikar, A.Sette, J.Sidney, K.Doege, and E.Cairns (2007).
The influence of MHC class II molecules containing the rheumatoid arthritis shared epitope on the immune response to aggrecan G1 and its peptides.
  Scand J Immunol, 65, 444-452.  
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.  
17041605 E.S.Huseby, F.Crawford, J.White, P.Marrack, and J.W.Kappler (2006).
Interface-disrupting amino acids establish specificity between T cell receptors and complexes of major histocompatibility complex and peptide.
  Nat Immunol, 7, 1191-1199.  
16623770 F.Crawford, K.R.Jordan, B.Stadinski, Y.Wang, E.Huseby, P.Marrack, J.E.Slansky, and J.W.Kappler (2006).
Use of baculovirus MHC/peptide display libraries to characterize T-cell receptor ligands.
  Immunol Rev, 210, 156-170.  
16762555 L.Holm, R.Bockermann, E.Wellner, J.Bäcklund, R.Holmdahl, and J.Kihlberg (2006).
Side-chain and backbone amide bond requirements for glycopeptide stimulation of T-cells obtained in a mouse model for rheumatoid arthritis.
  Bioorg Med Chem, 14, 5921-5932.  
16051149 E.S.Huseby, J.White, F.Crawford, T.Vass, D.Becker, C.Pinilla, P.Marrack, and J.W.Kappler (2005).
How the T cell repertoire becomes peptide and MHC specific.
  Cell, 122, 247-260.  
16239517 M.A.Bergman, L.A.Cummings, R.C.Alaniz, L.Mayeda, I.Fellnerova, and B.T.Cookson (2005).
CD4+-T-cell responses generated during murine Salmonella enterica serovar Typhimurium infection are directed towards multiple epitopes within the natural antigen FliC.
  Infect Immun, 73, 7226-7235.  
15094798 F.Crawford, E.Huseby, J.White, P.Marrack, and J.W.Kappler (2004).
Mimotopes for alloreactive and conventional T cells in a peptide-MHC display library.
  PLoS Biol, 2, E90.  
15056041 V.Apostolopoulos, and E.Lazoura (2004).
Noncanonical peptides in complex with MHC class I.
  Expert Rev Vaccines, 3, 151-162.  
15331779 Z.Zavala-Ruiz, I.Strug, B.D.Walker, P.J.Norris, and L.J.Stern (2004).
A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition.
  Proc Natl Acad Sci U S A, 101, 13279-13284.
PDB codes: 1sje 1sjh
15489166 Z.Zavala-Ruiz, I.Strug, M.W.Anderson, J.Gorski, and L.J.Stern (2004).
A polymorphic pocket at the P10 position contributes to peptide binding specificity in class II MHC proteins.
  Chem Biol, 11, 1395-1402.
PDB codes: 1t5w 1t5x
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.