1UXW

CRYSTAL STRUCTURE OF HLA-B*2709 COMPLEXED WITH THE LATENT MEMBRANE PROTEIN 2 PEPTIDE (LMP2) OF EPSTEIN-BARR VIRUS

Summary for 1UXW

• Entry DOI: 10.2210/pdb1uxw/pdb
• Related: 1A1M 1A1N 1A1O 1A6Z 1A9B 1A9E 1AGB 1AGC 1AGD 1AGE 1AGF 1AKJ 1AO7 1B0G 1B0R 1BD2 1C16 1CE6 1CG9 1DE4 1DUY 1DUZ 1E27 1E28 1EEY 1EEZ 1EFX 1EXU 1GZP 1GZQ 1HHG 1HHH 1HHI 1HHJ 1HHK 1HLA 1HSA 1HSB 1I1F 1I1Y 1I4F 1I7R 1I7T 1I7U 1IM3 1IM9 1JF1 1JGD 1JGE 1JHT 1JNJ 1K5N 1KPR 1KTL 1LDS 1LP9 1M05 1M6O 1MHE 1MI5 1OF2 1OGA 1OGT 1ONQ 1P7Q 1QEW 1QLF 1QQD 1QR1 1QRN 1QSE 1QSF 1TMC 1UQS 1UR7 1UXS 2CLR 2HLA 3HLA
• Descriptor: HLA CLASS I HISTOCOMPATIBILITY ANTIGEN B-27 ALPHA CHAIN, BETA-2-MICROGLOBULIN, GENE TERMINAL PROTEIN (MEMBRANE PROTEIN LMP-2A/LMP-2B), ... (5 entities in total)
• Functional Keywords: immune system-peptide complex, complex (antigen-peptide), immune system, mhc (major histocompatibility complex), hla- b*2709, immune system/peptide
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Membrane; Single-pass type I membrane protein: P03989; Secreted: P01884; Isoform LMP2A: Host cell membrane; Multi- pass membrane protein. Isoform LMP2B: Host endomembrane system; Multi-pass membrane protein: P13285
• Total number of polymer chains: 3
• Total formula weight: 45594.63

Authors

Hulsmeyer, M.,Kozerski, C.,Fiorillo, M.T.,Sorrentino, R.,Saenger, W.,Ziegler, A.,Uchanska-Ziegler, B. (deposition date: 2004-03-01, release date: 2004-11-09, Last modification date: 2023-12-13)

Primary citation

Fiorillo, M.T.,Ruckert, C.,Hulsmeyer, M.,Sorrentino, R.,Saenger, W.,Ziegler, A.,Uchanska-Ziegler, B.
Allele-Dependent Similarity between Viral and Self-Peptide Presentation by Hla-B27 Subtypes
J.Biol.Chem., 280:2962-, 2005

PubMed Abstract: Molecular mimicry is discussed as a possible mechanism that may contribute to the development of autoimmune diseases. It could also be involved in the differential association of the human major histocompatibility subtypes HLA-B(*)2705 and HLA-B(*)2709 with ankylosing spondylitis. These two subtypes differ only in residue 116 of the heavy chain (Asp in B(*)2705 and His in B(*)2709), but the reason for the differential disease association is not understood. Using x-ray crystallography, we show here that the viral peptide pLMP2 (RRRWRRLTV, derived from latent membrane protein 2 (residues 236-244) of Epstein-Barr virus) is presented by the B(*)2705 and B(*)2709 molecules in two drastically deviating conformations. Extensive structural similarity between pLMP2 and the self-peptide pVIPR (RRKWRRWHL, derived from vasoactive intestinal peptide type 1 receptor (residues 400-408)) is observed only when the peptides are presented by B(*)2705 because of a salt bridge between Arg(5) of both peptides and the subtype-specific heavy chain residue Asp(116). Combined with functional studies using pLMP2/pVIPR-cross-reactive cytotoxic T cell lines and clones, together with target cells presenting these peptides or a modified peptide analogue, our results reveal that a pathogen-derived peptide can exhibit major histocompatibility complex class I subtype-dependent, drastically distinct binding modes. Furthermore, the results demonstrate that molecular mimicry between pLMP2 and pVIPR in the HLA-B27 context is an allele-dependent property.

PubMed: 15537660
DOI: 10.1074/JBC.M410807200

Experimental method

X-RAY DIFFRACTION (1.71 Å)