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PDBsum entry 1sjh

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protein Protein-protein interface(s) links
Immune system PDB id
1sjh
Jmol
Contents
Protein chains
179 a.a. *
190 a.a. *
13 a.a. *
230 a.a. *
Waters ×252
* Residue conservation analysis
PDB id:
1sjh
Name: Immune system
Title: Hla-dr1 complexed with a 13 residue HIV capsid peptide
Structure: Hla class ii histocompatibility antigen, dr alpha chain. Chain: a. Fragment: extracellular domain of hla-dra 0101. Synonym: mhc class ii antigen dra. Engineered: yes. Hla class ii histocompatibility antigen, drb1-1 beta chain. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-dra. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: hla-drb1. Synthetic: yes. Other_details: synthesized peptide with sequence from
Biol. unit: Dodecamer (from PDB file)
Resolution:
2.25Å     R-factor:   0.220     R-free:   0.245
Authors: Z.Zavala-Ruiz,I.Strug,B.D.Walker,P.J.Norris,L.J.Stern
Key ref:
Z.Zavala-Ruiz et al. (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. PubMed id: 15331779 DOI: 10.1073/pnas.0403371101
Date:
03-Mar-04     Release date:   17-Aug-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain
Seq:
Struc:
254 a.a.
179 a.a.
Protein chain
Pfam   ArchSchema ?
P04229  (2B11_HUMAN) -  HLA class II histocompatibility antigen, DRB1-1 beta chain
Seq:
Struc:
266 a.a.
190 a.a.
Protein chain
Pfam   ArchSchema ?
P12495  (GAG_HV1Z2) -  Gag polyprotein
Seq:
Struc:
501 a.a.
13 a.a.
Protein chain
Pfam   ArchSchema ?
P0A0L5  (ENTC3_STAAU) -  Enterotoxin type C-3
Seq:
Struc:
266 a.a.
230 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     immune response   3 terms 

 

 
DOI no: 10.1073/pnas.0403371101 Proc Natl Acad Sci U S A 101:13279-13284 (2004)
PubMed id: 15331779  
 
 
A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition.
Z.Zavala-Ruiz, I.Strug, B.D.Walker, P.J.Norris, L.J.Stern.
 
  ABSTRACT  
 
T cells generally recognize peptide antigens bound to MHC proteins through contacts with residues found within or immediately flanking the seven- to nine-residue sequence accommodated in the MHC peptide-binding groove. However, some T cells require peptide residues outside this region for activation, the structural basis for which is unknown. Here, we have investigated a HIV Gag-specific T cell clone that requires an unusually long peptide antigen for activation. The crystal structure of a minimally antigenic 16-mer bound to HLA-DR1 shows that the peptide C-terminal region bends sharply into a hairpin turn as it exits the binding site, orienting peptide residues outside the MHC-binding region in position to interact with a T cell receptor. Peptide truncation and substitution studies show that both the hairpin turn and the extreme C-terminal residues are required for T cell activation. These results demonstrate a previously unrecognized mode of MHC-peptide-T cell receptor interaction.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Crystal structures of DR1/Gag[PP16]/SEC3 and DR1/Gag[PG13]/SEC3. (A) A |2 F[o] - F[c]| electron density map calculated by using model phases and contoured at 1 for the Gag[PP16] complex in the vicinity of the peptide. Carbon atoms are yellow, nitrogen atoms are blue, and oxygen atoms are red. (B) Corresponding map of the Gag[PG13] complex, but with carbon atoms being green. (C) Surface of HLA-DR1 showing superposition of bound Gag[PP16] (yellow) and Gag[PG13] (green) peptides. (D and E) Difference Fourier map|F[Gag[PP16]] - F[Gag[PG13]]| calculated by using Gag[PP16] model phases, contoured at 4 , with positive (Gag[PP16]) density in yellow and negative (Gag[PG13]) density in green, overlaid with the Gag[PP16] peptide (D) or the Gag[PG13] peptide (E). No significant positive or negative difference peaks were observed outside this region.
Figure 3.
Fig. 3. A type II -turn at the C-terminal region of the Gag[PP16] peptide. (A) C-terminal region of the DR1 peptide-binding site with bound Gag[PP16] peptide showing conserved MHC peptide hydrogen bonds. Conserved MHC peptide hydrogen bonds in this region are shown as gray dashed lines, with the Gag[PP16] intraturn hydrogen bond between the nitrogen of Ala (P12) and the carbonyl oxygen of Ser (P9) shown as a red dashed line. (B) Closeup view of the Gag[PP16] hairpin, showing the intraturn hydrogen bond and - values characteristic of a type II -turn. (C) Alignment of HLA-DR crystal structures exhibiting ordered peptide density beyond P10. Complexes were aligned by least-squares fitting of 1 and 1 domains. Peptides are shown as C traces. DR1/TP1 is red (PDB ID code 1KLU [PDB] ), DR2a/MBP is blue (PDB ID code 1FV1 [PDB] ), DR3/CLIP is magenta (PDB ID code 1A6A [PDB] ), DR1/Ha is cyan (PDB ID code 1DLH [PDB] ), DR2a/EBV is gray (PDB ID code 1H15 [PDB] ), and DR4/collagen is orange (PDB ID code 2SEB [PDB] ).
 
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18545669 C.A.Painter, A.Cruz, G.E.López, L.J.Stern, and Z.Zavala-Ruiz (2008).
Model for the peptide-free conformation of class II MHC proteins.
  PLoS ONE, 3, e2403.  
18573126 M.A.Juliarena, M.Poli, L.Sala, C.Ceriani, S.Gutierrez, G.Dolcini, E.M.Rodríguez, B.Mariño, C.Rodríguez-Dubra, and E.N.Esteban (2008).
Association of BLV infection profiles with alleles of the BoLA-DRB3.2 gene.
  Anim Genet, 39, 432-438.  
17937498 J.M.Calvo-Calle, I.Strug, M.D.Nastke, S.P.Baker, and L.J.Stern (2007).
Human CD4+ T cell epitopes from vaccinia virus induced by vaccination or infection.
  PLoS Pathog, 3, 1511-1529.  
17389359 Y.Mimura, Y.Mimura-Kimura, K.Doores, D.Golgher, B.G.Davis, R.A.Dwek, P.M.Rudd, and T.Elliott (2007).
Folding of an MHC class II-restricted tumor antigen controls its antigenicity via MHC-guided processing.
  Proc Natl Acad Sci U S A, 104, 5983-5988.  
16868084 I.Durinovic-Belló, S.Rosinger, J.A.Olson, M.Congia, R.C.Ahmad, M.Rickert, J.Hampl, H.Kalbacher, J.W.Drijfhout, E.D.Mellins, S.Al Dahouk, T.Kamradt, M.J.Maeurer, C.Nhan, B.O.Roep, B.O.Boehm, C.Polychronakos, G.T.Nepom, W.Karges, H.O.McDevitt, and G.Sønderstrup (2006).
DRB1*0401-restricted human T cell clone specific for the major proinsulin73-90 epitope expresses a down-regulatory T helper 2 phenotype.
  Proc Natl Acad Sci U S A, 103, 11683-11688.  
17105666 J.Salomon, and D.R.Flower (2006).
Predicting Class II MHC-Peptide binding: a kernel based approach using similarity scores.
  BMC Bioinformatics, 7, 501.  
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.  
16294349 S.L.Dong, M.Löweneck, T.E.Schrader, W.J.Schreier, W.Zinth, L.Moroder, and C.Renner (2006).
A photocontrolled beta-hairpin peptide.
  Chemistry, 12, 1114-1120.  
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.  
16186824 F.E.Tynan, S.R.Burrows, A.M.Buckle, C.S.Clements, N.A.Borg, J.J.Miles, T.Beddoe, J.C.Whisstock, M.C.Wilce, S.L.Silins, J.M.Burrows, L.Kjer-Nielsen, L.Kostenko, A.W.Purcell, J.McCluskey, and J.Rossjohn (2005).
T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I-bound peptide.
  Nat Immunol, 6, 1114-1122.
PDB code: 2ak4
16181344 S.B.Lovitch, and E.R.Unanue (2005).
Conformational isomers of a peptide-class II major histocompatibility complex.
  Immunol Rev, 207, 293-313.  
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.