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PDBsum entry 1k5n
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Immune system PDB id
1k5n

 

 

 

 

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Contents
Protein chains
276 a.a. *
100 a.a. *
Ligands
GLY-ARG-PHE-ALA-
ALA-ALA-ILE-ALA-
LYS
GOL ×2
Waters ×959
* Residue conservation analysis
PDB id:
1k5n
Name: Immune system
Title: Hla-b 2709 Bound to nona-peptide m9
Structure: Major histocompatibility complex molecule hla-b 2709. Chain: a. Fragment: hla-b 2709 Heavy chain, extracellular domain. Synonym: lymphocyte antigen hla-b27. Engineered: yes. Beta-2-microglobulin, light chain. Chain: b. Engineered: yes. Nonameric model peptide m9.
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 synthesised.
Biol. unit: Trimer (from PQS)
Resolution:
1.09Å     R-factor:   0.123     R-free:   0.148
Authors: M.Hulsmeyer,R.C.Hillig,A.Volz,M.Ruhl,W.Schroder,W.Saenger,A.Ziegler, B.Uchanska-Ziegler
Key ref:
M.Hülsmeyer et al. (2002). HLA-B27 subtypes differentially associated with disease exhibit subtle structural alterations. J Biol Chem, 277, 47844-47853. PubMed id: 12244049 DOI: 10.1074/jbc.M206392200
Date:
11-Oct-01     Release date:   30-Oct-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01889  (1B07_HUMAN) -  HLA class I histocompatibility antigen, B alpha chain from Homo sapiens
Seq:
Struc: 		362 a.a.
276 a.a.*
Protein chain
Pfam   ArchSchema ?
P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens
Seq:
Struc: 		119 a.a.
100 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 21 residue positions (black crosses)

 

 
DOI no: 10.1074/jbc.M206392200 J Biol Chem 277:47844-47853 (2002)
PubMed id: 12244049  
 
 
HLA-B27 subtypes differentially associated with disease exhibit subtle structural alterations.
M.Hülsmeyer, R.C.Hillig, A.Volz, M.Rühl, W.Schröder, W.Saenger, A.Ziegler, B.Uchanska-Ziegler.
 
  ABSTRACT  
 
The reasons for the association of the human major histocompatibility complex protein HLA-B27 with spondyloarthropathies are unknown. To uncover the underlying molecular causes, we determined the crystal structures of the disease-associated B*2705 and the nonassociated B*2709 subtypes complexed with the same nonapeptide (GRFAAAIAK). Both differ in only one residue (Asp(116) and His(116), respectively) in the F-pocket that accommodates the peptide C terminus. Several different effects of the Asp(116) --> His replacement are observed. The bulkier His(116) induces a movement of peptide C-terminal pLys(9), allowing the formation of a novel salt bridge to Asp(77), whereas the salt bridge between pLys(9) and Asp(116) is converted into a hydrogen bond with His(116). His(116) but not Asp(116) adopts two alternative conformations, one of which leads to breakage of hydrogen bonds. Water molecules near residue 116 differ with regard to number, position, and contacts made. Furthermore, F-pocket atoms exhibit higher B-factors in B*2709 than in B*2705, indicating an increased flexibility of the entire region in the former subtype. These changes induce subtle peptide conformational alterations that may be responsible for the immunobiological differences between these HLA-B27 subtypes.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Representative section of the 2F[o] F[c] electron density map of B*2709·m9 at 1.09 Å contoured at 1.5 . The figure shows the conserved pentagonal hydrogen bonding network (indicated with dotted lines), which fixes the N terminus of the peptide to the binding groove. 		Figure 2.
Fig. 2. Overall protein fold and peptide binding groove of HLA-B*2705·m9 and B*2709·m9. A, ribbon representation of HLA-B*2709·m9 (HC in blue, [2]m in green, peptide as ball-and-stick model in red, and disulfide bridges and Cys67 in yellow). B, superimposition of the peptide binding grooves of B*2705·m9, B*2709·m9, and B*2705·ARA[7] (PDB entry 1hsa). Because the binding grooves are highly similar, only the backbone of the HC of B*2705·m9 is depicted (ribbon representation). Peptides are shown as C[ ]traces, m9 from B*2705 in blue, m9 from B*2709 in cyan, and ARA[7] in yellow.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 47844-47853) copyright 2002.  
  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.
PDB code: 3lv3
  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.  
21543847 R.M.McMahon, L.Friis, C.Siebold, M.A.Friese, L.Fugger, and E.Y.Jones (2011).
Structure of HLA-A*0301 in complex with a peptide of proteolipid protein: insights into the role of HLA-A alleles in susceptibility to multiple sclerosis.
  Acta Crystallogr D Biol Crystallogr, 67, 447-454.
PDB code: 2xpg
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.  
20946671 V.Stanevicha, J.Eglite, D.Zavadska, A.Sochnevs, A.Lazareva, D.Guseinova, R.Shantere, and D.Gardovska (2010).
HLA B27 allele types in homogeneous groups of juvenile idiopathic arthritis patients in Latvia.
  Pediatr Rheumatol Online J, 8, 26.  
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
18549801 D.Chessman, L.Kostenko, T.Lethborg, A.W.Purcell, N.A.Williamson, Z.Chen, L.Kjer-Nielsen, N.A.Mifsud, B.D.Tait, R.Holdsworth, C.A.Almeida, D.Nolan, W.A.Macdonald, J.K.Archbold, A.D.Kellerher, D.Marriott, S.Mallal, M.Bharadwaj, J.Rossjohn, and J.McCluskey (2008).
Human leukocyte antigen class I-restricted activation of CD8+ T cells provides the immunogenetic basis of a systemic drug hypersensitivity.
  Immunity, 28, 822-832.
PDB code: 2rfx
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.  
18007679 N.J.Felix, and P.M.Allen (2007).
Specificity of T-cell alloreactivity.
  Nat Rev Immunol, 7, 942-953.  
  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.  
16470819 A.J.Bordner, and R.Abagyan (2006).
Ab initio prediction of peptide-MHC binding geometry for diverse class I MHC allotypes.
  Proteins, 63, 512-526.  
16738940 D.H.Bos, and B.Waldman (2006).
Polymorphism, natural selection, and structural modeling of class Ia MHC in the African clawed frog (Xenopus laevis).
  Immunogenetics, 58, 433-442.  
16677075 K.Saleki, N.Hartigan, M.Lith, N.Bulleid, and A.M.Benham (2006).
Differential oxidation of HLA-B2704 and HLA-B2705 in lymphoblastoid and transfected adherent cells.
  Antioxid Redox Signal, 8, 292-299.  
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.  
16354304 B.A.Manjasetty, F.H.Niesen, C.Scheich, Y.Roske, F.Goetz, J.Behlke, V.Sievert, U.Heinemann, and K.Büssow (2005).
X-ray structure of engineered human Aortic Preferentially Expressed Protein-1 (APEG-1).
  BMC Struct Biol, 5, 21.
PDB code: 1u2h
  16511044 B.Loll, A.Zawacka, J.Biesiadka, C.Rückert, A.Volz, W.Saenger, B.Uchanska-Ziegler, and A.Ziegler (2005).
Purification, crystallization and preliminary X-ray diffraction analysis of the human major histocompatibility antigen HLA-B*2703 complexed with a viral peptide and with a self-peptide.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 372-374.  
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.  
15871042 R.Sainudiin, W.S.Wong, K.Yogeeswaran, J.B.Nasrallah, Z.Yang, and R.Nielsen (2005).
Detecting site-specific physicochemical selective pressures: applications to the Class I HLA of the human major histocompatibility complex and the SRK of the plant sporophytic self-incompatibility system.
  J Mol Evol, 60, 315-326.  
15014909 E.B.Starikov, E.B.Starikow, L.Nilsson, and M.Hülsmeyer (2004).
A single residue exchange between two HLA-B27 alleles triggers increased peptide flexibility.
  Eur Biophys J, 33, 651-655.  
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.  
14734527 M.Hülsmeyer, M.T.Fiorillo, F.Bettosini, R.Sorrentino, W.Saenger, A.Ziegler, and B.Uchanska-Ziegler (2004).
Dual, HLA-B27 subtype-dependent conformation of a self-peptide.
  J Exp Med, 199, 271-281.
PDB codes: 1of2 1ogt
12547503 B.Uchanska-Ziegler, and A.Ziegler (2003).
Ankylosing spondylitis: a beta2m-deposition disease?
  Trends Immunol, 24, 73-76.  
12939341 W.A.Macdonald, A.W.Purcell, N.A.Mifsud, L.K.Ely, D.S.Williams, L.Chang, J.J.Gorman, C.S.Clements, L.Kjer-Nielsen, D.M.Koelle, S.R.Burrows, B.D.Tait, R.Holdsworth, A.G.Brooks, G.O.Lovrecz, L.Lu, J.Rossjohn, and J.McCluskey (2003).
A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition.
  J Exp Med, 198, 679-691.
PDB codes: 1m6o 1n2r
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.

 

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