3B3I

Citrullination-dependent differential presentation of a self-peptide by HLA-B27 subtypes

Summary for 3B3I

• Entry DOI: 10.2210/pdb3b3i/pdb
• Related: 1OF2 1OGT
• Descriptor: HLA class I histocompatibility antigen, B-27 alpha chain, Beta-2-microglobulin, Vasoactive intestinal polypeptide receptor 1, ... (5 entities in total)
• Functional Keywords: hla-b2709, ankylosing spondylitis, glycoprotein, host-virus interaction, immune response, membrane, mhc i, transmembrane, disease mutation, glycation, immunoglobulin domain, pyrrolidone carboxylic acid, secreted, g-protein coupled receptor, phosphorylation, receptor, transducer, protein binding, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P03989; Secreted . Note=(Microbial infection) In the presence of M: P61769; Cell membrane; Multi-pass membrane protein: P32241
• Total number of polymer chains: 3
• Total formula weight: 45782.81

Authors

Beltrami, A.,Rossmann, M.,Fiorillo, M.T.,Paladini, F.,Sorrentino, R.,Saenger, W.,Kumar, P.,Ziegler, A.,Uchanska-Ziegler, B. (deposition date: 2007-10-22, release date: 2008-07-22, Last modification date: 2024-10-30)

Primary citation

Beltrami, A.,Rossmann, M.,Fiorillo, M.T.,Paladini, F.,Sorrentino, R.,Saenger, W.,Kumar, P.,Ziegler, A.,Uchanska-Ziegler, B.
Citrullination-dependent differential presentation of a self-peptide by HLA-B27 subtypes.
J.Biol.Chem., 283:27189-27199, 2008

PubMed Abstract: Inflammatory processes are accompanied by the posttranslational modification of certain arginine residues within proteins to yield citrulline, although it is largely unknown how this modification influences antigen presentation. We employed crystallographic and functional studies to investigate whether the exchange of arginine to citrulline affects the display of a peptide by two human major histocompatibility antigen class I subtypes, HLA-B(*)2705 and HLA-B(*)2709. Both differ only in residue 116 within the peptide binding groove despite their differential association with ankylosing spondylitis, an inflammatory rheumatic disorder. The crystal structures described here show that a modified self-peptide, pVIPR-U5 (RRKWURWHL; U = citrulline), is presented by the two HLA-B27 molecules in distinct conformations. These binding modes differ not only drastically from each other but also from the conformations exhibited by the non-citrullinated peptide in a given subtype. The differential reactivity of HLA-B27-restricted cytotoxic T cells with modified or unmodified pVIPR supports the structural findings and shows that the presentation of citrullinated peptides has the potential to influence immune responses.

PubMed: 18650441
DOI: 10.1074/jbc.M802818200

Experimental method

X-RAY DIFFRACTION (1.86 Å)