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PDBsum entry 1fng

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protein ligands Protein-protein interface(s) links
Immune system PDB id
1fng
Jmol
Contents
Protein chains
182 a.a. *
213 a.a. *
Ligands
NAG ×6
Waters ×507
* Residue conservation analysis
PDB id:
1fng
Name: Immune system
Title: Histocompatibility antigen
Structure: Protein (mhc class ii i-ek, alpha chain). Chain: a, c. Fragment: soluble ecto-domain. Engineered: yes. Protein (mhc class ii i-ek, beta chain). Chain: b, d. Fragment: soluble ecto-domain plus covalently attached hb p engineered: yes. Other_details: with covalently bound hb peptide
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_taxid: 7108
Biol. unit: Octamer (from PQS)
Resolution:
1.90Å     R-factor:   0.221     R-free:   0.254
Authors: M.J.Miley,C.A.Nelson,D.H.Fremont
Key ref: G.J.Kersh et al. (2001). Structural and functional consequences of altering a peptide MHC anchor residue. J Immunol, 166, 3345-3354. PubMed id: 11207290
Date:
21-Aug-00     Release date:   07-Mar-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04224  (HA22_MOUSE) -  H-2 class II histocompatibility antigen, E-K alpha chain
Seq:
Struc:
255 a.a.
182 a.a.
Protein chains
Pfam   ArchSchema ?
P02089  (HBB2_MOUSE) -  Hemoglobin subunit beta-2
Seq:
Struc:
147 a.a.
213 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 65 residue positions (black crosses)

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

 

 
J Immunol 166:3345-3354 (2001)
PubMed id: 11207290  
 
 
Structural and functional consequences of altering a peptide MHC anchor residue.
G.J.Kersh, M.J.Miley, C.A.Nelson, A.Grakoui, S.Horvath, D.L.Donermeyer, J.Kappler, P.M.Allen, D.H.Fremont.
 
  ABSTRACT  
 
To better understand TCR discrimination of multiple ligands, we have analyzed the crystal structures of two Hb peptide/I-E(k) complexes that differ by only a single amino acid substitution at the P6 anchor position within the peptide (E73D). Detailed comparison of multiple independently determined structures at 1.9 A resolution reveals that removal of a single buried methylene group can alter a critical portion of the TCR recognition surface. Significant variance was observed in the peptide P5-P8 main chain as well as a rotamer difference at LeuP8, approximately 10 A distal from the substitution. No significant variations were observed in the conformation of the two MHC class II molecules. The ligand alteration results in two peptide/MHC complexes that generate bulk T cell responses that are distinct and essentially nonoverlapping. For the Hb-specific T cell 3.L2, substitution reduces the potency of the ligand 1000-fold. Soluble 3.L2 TCR binds the two peptide/MHC complexes with similar affinity, although with faster kinetics. These results highlight the role of subtle variations in MHC Ag presentation on T cell activation and signaling.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
20007533 C.K.Baumgartner, A.Ferrante, M.Nagaoka, J.Gorski, and L.P.Malherbe (2010).
Peptide-MHC class II complex stability governs CD4 T cell clonal selection.
  J Immunol, 184, 573-581.  
19904613 J.J.Sabatino, K.M.Rosenthal, and B.D.Evavold (2010).
Manipulating antigenic ligand strength to selectively target myelin-reactive CD4+ T cells in EAE.
  J Neuroimmune Pharmacol, 5, 176-188.  
20333301 M.A.Patarroyo, A.Bermúdez, C.López, G.Yepes, and M.E.Patarroyo (2010).
3D analysis of the TCR/pMHCII complex formation in monkeys vaccinated with the first peptide inducing sterilizing immunity against human malaria.
  PLoS One, 5, e9771.  
20711359 S.A.Valkenburg, S.Gras, C.Guillonneau, N.L.La Gruta, P.G.Thomas, A.W.Purcell, J.Rossjohn, P.C.Doherty, S.J.Turner, and K.Kedzierska (2010).
Protective efficacy of cross-reactive CD8+ T cells recognising mutant viral epitopes depends on peptide-MHC-I structural interactions and T cell activation threshold.
  PLoS Pathog, 6, 0.
PDB code: 3ftg
20334923 S.P.Persaud, D.L.Donermeyer, K.S.Weber, D.M.Kranz, and P.M.Allen (2010).
High-affinity T cell receptor differentiates cognate peptide-MHC and altered peptide ligands with distinct kinetics and thermodynamics.
  Mol Immunol, 47, 1793-1801.  
19801984 W.L.Lo, N.J.Felix, J.J.Walters, H.Rohrs, M.L.Gross, and P.M.Allen (2009).
An endogenous peptide positively selects and augments the activation and survival of peripheral CD4+ T cells.
  Nat Immunol, 10, 1155-1161.  
18271720 C.Bidot, F.Gruy, C.S.Haudin, F.El Hentati, B.Guy, and C.Lambert (2008).
Mathematical modeling of T-cell activation kinetic.
  J Comput Biol, 15, 105-128.  
17363906 C.Mazza, N.Auphan-Anezin, C.Gregoire, A.Guimezanes, C.Kellenberger, A.Roussel, A.Kearney, P.A.van der Merwe, A.M.Schmitt-Verhulst, and B.Malissen (2007).
How much can a T-cell antigen receptor adapt to structurally distinct antigenic peptides?
  EMBO J, 26, 1972-1983.
PDB code: 2ol3
17398114 K.W.Wucherpfennig, P.M.Allen, F.Celada, I.R.Cohen, R.De Boer, K.C.Garcia, B.Goldstein, R.Greenspan, D.Hafler, P.Hodgkin, E.S.Huseby, D.C.Krakauer, D.Nemazee, A.S.Perelson, C.Pinilla, R.K.Strong, and E.E.Sercarz (2007).
Polyspecificity of T cell and B cell receptor recognition.
  Semin Immunol, 19, 216-224.  
17322886 N.J.Felix, D.L.Donermeyer, S.Horvath, J.J.Walters, M.L.Gross, A.Suri, and P.M.Allen (2007).
Alloreactive T cells respond specifically to multiple distinct peptide-MHC complexes.
  Nat Immunol, 8, 388-397.  
18007679 N.J.Felix, and P.M.Allen (2007).
Specificity of T-cell alloreactivity.
  Nat Rev Immunol, 7, 942-953.  
17719062 O.Y.Borbulevych, F.K.Insaidoo, T.K.Baxter, D.J.Powell, L.A.Johnson, N.P.Restifo, and B.M.Baker (2007).
Structures of MART-126/27-35 Peptide/HLA-A2 complexes reveal a remarkable disconnect between antigen structural homology and T cell recognition.
  J Mol Biol, 372, 1123-1136.
PDB codes: 2gt9 2gtw 2gtz 2guo
17719490 V.Mitaksov, S.M.Truscott, L.Lybarger, J.M.Connolly, T.H.Hansen, and D.H.Fremont (2007).
Structural engineering of pMHC reagents for T cell vaccines and diagnostics.
  Chem Biol, 14, 909-922.
PDB codes: 2qri 2qrs 2qrt
17291278 Y.H.Chien, and Y.Konigshofer (2007).
Antigen recognition by gammadelta T cells.
  Immunol Rev, 215, 46-58.  
16791622 M.E.Patarroyo, G.Cifuentes, and J.Baquero (2006).
Comparative molecular and three-dimensional analysis of the peptide-MHC II binding region in both human and Aotus MHC-DRB molecules confirms their usefulness in antimalarial vaccine development.
  Immunogenetics, 58, 598-606.  
16216327 P.J.Norris, J.D.Stone, N.Anikeeva, J.W.Heitman, I.C.Wilson, D.F.Hirschkorn, M.J.Clark, H.F.Moffett, T.O.Cameron, Y.Sykulev, L.J.Stern, and B.D.Walker (2006).
Antagonism of HIV-specific CD4+ T cells by C-terminal truncation of a minimum epitope.
  Mol Immunol, 43, 1349-1357.  
16181342 A.J.Sant, F.A.Chaves, S.A.Jenks, K.A.Richards, P.Menges, J.M.Weaver, and C.A.Lazarski (2005).
The relationship between immunodominance, DM editing, and the kinetic stability of MHC class II:peptide complexes.
  Immunol Rev, 207, 261-278.  
16365315 K.S.Weber, D.L.Donermeyer, P.M.Allen, and D.M.Kranz (2005).
Class II-restricted T cell receptor engineered in vitro for higher affinity retains peptide specificity and function.
  Proc Natl Acad Sci U S A, 102, 19033-19038.  
  15814707 O.Y.Borbulevych, T.K.Baxter, Z.Yu, N.P.Restifo, and B.M.Baker (2005).
Increased immunogenicity of an anchor-modified tumor-associated antigen is due to the enhanced stability of the peptide/MHC complex: implications for vaccine design.
  J Immunol, 174, 4812-4820.
PDB codes: 1tvb 1tvh
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.  
15589168 D.A.Price, S.M.West, M.R.Betts, L.E.Ruff, J.M.Brenchley, D.R.Ambrozak, Y.Edghill-Smith, M.J.Kuroda, D.Bogdan, K.Kunstman, N.L.Letvin, G.Franchini, S.M.Wolinsky, R.A.Koup, and D.C.Douek (2004).
T cell receptor recognition motifs govern immune escape patterns in acute SIV infection.
  Immunity, 21, 793-803.  
15557346 M.J.Miley, I.Messaoudi, B.M.Metzner, Y.Wu, J.Nikolich-Zugich, and D.H.Fremont (2004).
Structural basis for the restoration of TCR recognition of an MHC allelic variant by peptide secondary anchor substitution.
  J Exp Med, 200, 1445-1454.
PDB codes: 1rjy 1rjz 1rk0 1rk1
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
12716452 J.A.Hill, D.Wang, A.M.Jevnikar, E.Cairns, and D.A.Bell (2003).
The relationship between predicted peptide-MHC class II affinity and T-cell activation in a HLA-DRbeta1*0401 transgenic mouse model.
  Arthritis Res Ther, 5, R40-R48.  
14511376 M.H.Torres, L.M.Salazar, M.Vanegas, F.Guzman, R.Rodriguez, Y.Silva, J.Rosas, and M.E.Patarroyo (2003).
Modified merozoite surface protein-1 peptides with short alpha helical regions are associated with inducing protection against malaria.
  Eur J Biochem, 270, 3946-3952.  
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.  
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
11877480 J.Hennecke, and D.C.Wiley (2002).
Structure of a complex of the human alpha/beta T cell receptor (TCR) HA1.7, influenza hemagglutinin peptide, and major histocompatibility complex class II molecule, HLA-DR4 (DRA*0101 and DRB1*0401): insight into TCR cross-restriction and alloreactivity.
  J Exp Med, 195, 571-581.
PDB code: 1j8h
12021307 M.A.Haque, P.Li, S.K.Jackson, H.M.Zarour, J.W.Hawes, U.T.Phan, M.Maric, P.Cresswell, and J.S.Blum (2002).
Absence of gamma-interferon-inducible lysosomal thiol reductase in melanomas disrupts T cell recognition of select immunodominant epitopes.
  J Exp Med, 195, 1267-1277.  
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
11481463 S.R.Riddell (2001).
Progress in cancer vaccines by enhanced self-presentation.
  Proc Natl Acad Sci U S A, 98, 8933-8935.  
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.