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PDBsum entry 1jgd

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protein ligands Protein-protein interface(s) links
Immune system PDB id
1jgd
Jmol
Contents
Protein chains
276 a.a. *
100 a.a. *
Ligands
ARG-ARG-LEU-LEU-
ARG-GLY-HIS-ASN-
GLN-TYR
GOL
Waters ×452
* Residue conservation analysis
PDB id:
1jgd
Name: Immune system
Title: Hla-b 2709 Bound to deca-peptide s10r
Structure: Human lymphocyte antigen hla-b27. Chain: a. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes. Peptide s10r. Chain: c. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-b or hlab. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m. Synthetic: yes. Other_details: this peptide was chemically synthesized.
Biol. unit: Trimer (from PQS)
Resolution:
1.90Å     R-factor:   0.170     R-free:   0.194
Authors: R.C.Hillig,M.Huelsmeyer,W.Saenger,A.Volz,B.Uchanska-Ziegler,
Key ref:
R.C.Hillig et al. (2004). Thermodynamic and structural analysis of peptide- and allele-dependent properties of two HLA-B27 subtypes exhibiting differential disease association. J Biol Chem, 279, 652-663. PubMed id: 14555655 DOI: 10.1074/jbc.M307457200
Date:
25-Jun-01     Release date:   01-Jul-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P03989  (1B27_HUMAN) -  HLA class I histocompatibility antigen, B-27 alpha chain
Seq:
Struc:
362 a.a.
276 a.a.*
Protein chain
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin
Seq:
Struc:
119 a.a.
100 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   16 terms 
  Biological process     immune system process   22 terms 
  Biochemical function     protein binding     3 terms  

 

 
DOI no: 10.1074/jbc.M307457200 J Biol Chem 279:652-663 (2004)
PubMed id: 14555655  
 
 
Thermodynamic and structural analysis of peptide- and allele-dependent properties of two HLA-B27 subtypes exhibiting differential disease association.
R.C.Hillig, M.Hülsmeyer, W.Saenger, K.Welfle, R.Misselwitz, H.Welfle, C.Kozerski, A.Volz, B.Uchanska-Ziegler, A.Ziegler.
 
  ABSTRACT  
 
Selected HLA-B27 subtypes are associated with spondyloarthropathies, but the underlying mechanism is not understood. To explain this association in molecular terms, a comparison of peptide-dependent dynamic and structural properties of the differentially disease-associated subtypes HLA-B*2705 and HLA-B*2709 was carried out. These molecules differ only by a single amino acid at the floor of the peptide binding groove. The thermostabilities of a series of HLA-B27 molecules complexed with nonameric and decameric peptides were determined and revealed substantial differences depending on the subtype as well as the residues at the termini of the peptides. In addition we present the crystal structure of the B*2709 subtype complexed with a decameric peptide. This structure provides an explanation for the preference of HLA-B27 for a peptide with an N-terminal arginine as secondary anchor and the lack of preference for tyrosine as peptide C terminus in B*2709. The data show that differences in thermodynamic properties between peptide-complexed HLA-B27 subtypes are correlated with a variety of structural properties.
 
  Selected figure(s)  
 
Figure 2.
FIG. 2. Peptide electron density and differential conformations in the HLA-B27 binding groove. A, electron density map for the s10R peptide (F[o] - F[c] omit map, contoured at 3 , for the final model with the peptide omitted from map calculation). Superimposition of peptide binding grooves of HLA-B27 protein complexes in the top (B) and side view (C) orientation, with the C backbone conformation for s10R (red), m9 (blue, from B^*2709·m9, PDB entry 1k5n [PDB] ; cyan, from B^*2705·m9, PDB entry 1jge [PDB] ), and ARA[7] (yellow, B^*2705·ARA[7], PDB entry 1hsa [PDB] ), illustrating the stronger bulging of s10R out of the binding groove. In C, helix 2 is omitted for clarity.
Figure 7.
FIG. 7. HLA-B27-specific sandwich coordination of the secondary anchor pArg1. A, stereo figure showing the clamp stack involving pArg1 of the s10R peptide (red) and Arg-62, Glu-163, and Trp167 from the HC (green). The alternative conformation of Glu-163 is indicated in light green. Hydrogen bonds between Arg-62, Glu-163, pArg1, and Wat58 are indicated with dotted lines, and - -stacking and hydrophobic interactions by are indicated by stripes. B, the same region in the B^*2709·m9 complex (PDB entry 1jge [PDB] ). Because the N-terminal pArg1 is missing in m9, no stacking is present. Consequently, Trp-167 folds onto pGly1, and the Arg-62 side chain adopts a conformation parallel to helix 1. C and D, for comparison two murine MHC molecules are shown. Both feature a pArg1 but do not adopt the Arg-62-pArg1-Trp-167 sandwich conformation found in B^*2709·s10R. C, H-2Kb·VSV8, PDB entry 1bqh [PDB] , molecule 2. D, H-2D^d·HIV-1 (human immunodeficiency virus 1), PDB entry 1bii [PDB] .
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 652-663) copyright 2004.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21280120 B.Loll, C.Rückert, C.S.Hee, W.Saenger, B.Uchanska-Ziegler, and A.Ziegler (2011).
Loss of recognition by cross-reactive T cells and its relation to a C-terminus-induced conformational reorientation of an HLA-B*2705-bound peptide.
  Protein Sci, 20, 278-290.  
  21414141 H.Fabian, B.Loll, H.Huser, D.Naumann, B.Uchanska-Ziegler, and A.Ziegler (2011).
Influence of inflammation-related changes on conformational characteristics of HLA-B27 subtypes as detected by IR spectroscopy.
  FEBS J, 278, 1713-1727.  
21151886 C.S.Hee, S.Gao, B.Loll, M.M.Miller, B.Uchanska-Ziegler, O.Daumke, and A.Ziegler (2010).
Structure of a classical MHC class I molecule that binds "non-classical" ligands.
  PLoS Biol, 8, e1000557.
PDB codes: 3p73 3p77
20131248 H.Fabian, H.Huser, B.Loll, A.Ziegler, D.Naumann, and B.Uchanska-Ziegler (2010).
HLA-B27 heavy chains distinguished by a micropolymorphism exhibit differential flexibility.
  Arthritis Rheum, 62, 978-987.  
19553306 A.Wahl, W.McCoy, F.Schafer, W.Bardet, R.Buchli, D.H.Fremont, and W.H.Hildebrand (2009).
T-cell tolerance for variability in an HLA class I-presented influenza A virus epitope.
  J Virol, 83, 9206-9214.  
19201651 A.Ziegler, C.A.Müller, R.A.Böckmann, and B.Uchanska-Ziegler (2009).
Low-affinity peptides and T-cell selection.
  Trends Immunol, 30, 53-60.  
19617632 P.Kumar, A.Vahedi-Faridi, W.Saenger, E.Merino, J.A.López de Castro, B.Uchanska-Ziegler, and A.Ziegler (2009).
Structural basis for T cell alloreactivity among three HLA-B14 and HLA-B27 antigens.
  J Biol Chem, 284, 29784-29797.
PDB codes: 3bp4 3bp7 3bvn 3bxn
18166219 J.C.Davis, and P.J.Mease (2008).
Insights into the pathology and treatment of spondyloarthritis: from the bench to the clinic.
  Semin Arthritis Rheum, 38, 83.  
18489433 M.Marcilla, and J.A.López de Castro (2008).
Peptides: the cornerstone of HLA-B27 biology and pathogenetic role in spondyloarthritis.
  Tissue Antigens, 71, 495-506.  
17573425 K.Winkler, A.Winter, C.Rueckert, B.Uchanska-Ziegler, and U.Alexiev (2007).
Natural MHC class I polymorphism controls the pathway of peptide dissociation from HLA-B27 complexes.
  Biophys J, 93, 2743-2755.  
  17620730 P.Kumar, A.Vahedi-Faridi, E.Merino, J.A.López de Castro, A.Volz, A.Ziegler, W.Saenger, and B.Uchanska-Ziegler (2007).
Expression, purification and preliminary X-ray crystallographic analysis of the human major histocompatibility antigen HLA-B*1402 in complex with a viral peptide and with a self-peptide.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 631-634.  
17407096 S.Kollnberger, A.Chan, M.Y.Sun, L.Y.Chen, C.Wright, K.di Gleria, A.McMichael, and P.Bowness (2007).
Interaction of HLA-B27 homodimers with KIR3DL1 and KIR3DL2, unlike HLA-B27 heterotrimers, is independent of the sequence of bound peptide.
  Eur J Immunol, 37, 1313-1322.  
16783853 P.Gómez, V.Montserrat, M.Marcilla, A.Paradela, and J.A.de Castro (2006).
B*2707 differs in peptide specificity from B*2705 and B*2704 as much as from HLA-B27 subtypes not associated to spondyloarthritis.
  Eur J Immunol, 36, 1867-1881.  
16200602 M.N.Vázquez, and J.A.López de Castro (2005).
Similar cell surface expression of beta2-microglobulin-free heavy chains by HLA-B27 subtypes differentially associated with ankylosing spondylitis.
  Arthritis Rheum, 52, 3290-3299.  
15104674 J.A.Lopez de Castro, I.Alvarez, M.Marcilla, A.Paradela, M.Ramos, L.Sesma, and M.Vázquez (2004).
HLA-B27: a registry of constitutive peptide ligands.
  Tissue Antigens, 63, 424-445.  
15016342 J.D.Reveille (2004).
The genetic basis of spondyloarthritis.
  Curr Rheumatol Rep, 6, 117-125.  
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.