1of2

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|PDB= 1of2 |SIZE=350|CAPTION= <scene name='initialview01'>1of2</scene>, resolution 2.20&Aring;
|PDB= 1of2 |SIZE=350|CAPTION= <scene name='initialview01'>1of2</scene>, resolution 2.20&Aring;
|SITE= <scene name='pdbsite=AC1:Mn+Binding+Site+For+Chain+A'>AC1</scene>
|SITE= <scene name='pdbsite=AC1:Mn+Binding+Site+For+Chain+A'>AC1</scene>
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|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
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|LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>
|ACTIVITY=
|ACTIVITY=
|GENE=
|GENE=
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|DOMAIN=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1of2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1of2 OCA], [http://www.ebi.ac.uk/pdbsum/1of2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1of2 RCSB]</span>
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}}
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==Overview==
==Overview==
The products of the human leukocyte antigen subtypes HLA-B*2705 and HLA-B*2709 differ only in residue 116 (Asp vs. His) within the peptide binding groove but are differentially associated with the autoimmune disease ankylosing spondylitis (AS); HLA-B*2705 occurs in AS-patients, whereas HLA-B*2709 does not. The subtypes also generate differential T cell repertoires as exemplified by distinct T cell responses against the self-peptide pVIPR (RRKWRRWHL). The crystal structures described here show that pVIPR binds in an unprecedented dual conformation only to HLA-B*2705 molecules. In one binding mode, peptide pArg5 forms a salt bridge to Asp116, connected with drastically different interactions between peptide and heavy chain, contrasting with the second, conventional conformation, which is exclusively found in the case of B*2709. These subtype-dependent differences in pVIPR binding link the emergence of dissimilar T cell repertoires in individuals with HLA-B*2705 or HLA-B*2709 to the buried Asp116/His116 polymorphism and provide novel insights into peptide presentation by major histocompatibility antigens.
The products of the human leukocyte antigen subtypes HLA-B*2705 and HLA-B*2709 differ only in residue 116 (Asp vs. His) within the peptide binding groove but are differentially associated with the autoimmune disease ankylosing spondylitis (AS); HLA-B*2705 occurs in AS-patients, whereas HLA-B*2709 does not. The subtypes also generate differential T cell repertoires as exemplified by distinct T cell responses against the self-peptide pVIPR (RRKWRRWHL). The crystal structures described here show that pVIPR binds in an unprecedented dual conformation only to HLA-B*2705 molecules. In one binding mode, peptide pArg5 forms a salt bridge to Asp116, connected with drastically different interactions between peptide and heavy chain, contrasting with the second, conventional conformation, which is exclusively found in the case of B*2709. These subtype-dependent differences in pVIPR binding link the emergence of dissimilar T cell repertoires in individuals with HLA-B*2705 or HLA-B*2709 to the buried Asp116/His116 polymorphism and provide novel insights into peptide presentation by major histocompatibility antigens.
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==Disease==
 
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Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]], Hypoproteinemia, hypercatabolic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109700 109700]], Spondyloarthropathy, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142830 142830]]
 
==About this Structure==
==About this Structure==
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[[Category: Uchanska-Ziegler, B.]]
[[Category: Uchanska-Ziegler, B.]]
[[Category: Ziegler, A.]]
[[Category: Ziegler, A.]]
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[[Category: GOL]]
 
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[[Category: MN]]
 
[[Category: hla (human leukocyte antigen)]]
[[Category: hla (human leukocyte antigen)]]
[[Category: mhc (major histocompatibility complex)]]
[[Category: mhc (major histocompatibility complex)]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:09:59 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:44:21 2008''

Revision as of 19:44, 30 March 2008


PDB ID 1of2

Drag the structure with the mouse to rotate
, resolution 2.20Å
Sites:
Ligands: ,
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



CRYSTAL STRUCTURE OF HLA-B*2709 COMPLEXED WITH THE VASOACTIVE INTESTINAL PEPTIDE TYPE 1 RECEPTOR (VIPR) PEPTIDE (RESIDUES 400-408)


Overview

The products of the human leukocyte antigen subtypes HLA-B*2705 and HLA-B*2709 differ only in residue 116 (Asp vs. His) within the peptide binding groove but are differentially associated with the autoimmune disease ankylosing spondylitis (AS); HLA-B*2705 occurs in AS-patients, whereas HLA-B*2709 does not. The subtypes also generate differential T cell repertoires as exemplified by distinct T cell responses against the self-peptide pVIPR (RRKWRRWHL). The crystal structures described here show that pVIPR binds in an unprecedented dual conformation only to HLA-B*2705 molecules. In one binding mode, peptide pArg5 forms a salt bridge to Asp116, connected with drastically different interactions between peptide and heavy chain, contrasting with the second, conventional conformation, which is exclusively found in the case of B*2709. These subtype-dependent differences in pVIPR binding link the emergence of dissimilar T cell repertoires in individuals with HLA-B*2705 or HLA-B*2709 to the buried Asp116/His116 polymorphism and provide novel insights into peptide presentation by major histocompatibility antigens.

About this Structure

1OF2 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Dual, HLA-B27 subtype-dependent conformation of a self-peptide., Hulsmeyer M, Fiorillo MT, Bettosini F, Sorrentino R, Saenger W, Ziegler A, Uchanska-Ziegler B, J Exp Med. 2004 Jan 19;199(2):271-81. PMID:14734527

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