skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: X-ray diffraction analysis of crystals from the human major histocompatibility antigen HLA-B*2706 in complex with a viral peptide and with a self-peptide

Abstract

The crystallization of HLA-B*2706 in complex with two peptides is reported. The human leukocyte antigen (HLA) alleles HLA-B*2704 and HLA-B*2706 show an ethnically restricted distribution and are differentially associated with ankylosing spondylitis, with HLA-B*2706 lacking association with this autoimmune disease. However, the products of the two alleles differ by only two amino acids, at heavy-chain residues 114 (His in HLA-B*2704; Asp in HLA-B*2706) and 116 (Asp in HLA-B*2704; Tyr in HLA-B*2706). Both residues could be involved in contacting amino acids of a bound peptide, suggesting that peptides presented by these subtypes play a role in disease pathogenesis. Two HLA-B*2706–peptide complexes were crystallized using the hanging-drop vapour-diffusion method with PEG as precipitant. Data sets were collected to resolutions of 2.70 Å (viral peptide pLMP2, RRRWRRLTV; space group P2{sub 1}2{sub 1}2{sub 1}) and 1.83 Å (self-peptide pVIPR, RRKWRRWHL; space group P2{sub 1}). Using HLA-B*2705 complexed with the pGR peptide (RRRWHRWRL) as a search model, unambiguous molecular-replacement solutions were found for both HLA-B*2706 complexes.

Authors:
 [1]; ; ;  [2]; ;  [1]
  1. Institut für Immungenetik, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Humboldt-Universität zu Berlin, Spandauer Damm 130, 14050 Berlin (Germany)
  2. Institut für Chemie und Biochemie/Kristallographie, Freie Universität Berlin, Takustrasse 6, 14195 Berlin (Germany)
Publication Date:
OSTI Identifier:
22356206
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section F; Journal Volume: 61; Journal Issue: Pt 12; Other Information: PMCID: PMC1978159; PMID: 16511245; PUBLISHER-ID: en5140; OAI: oai:pubmedcentral.nih.gov:1978159; Copyright (c) International Union of Crystallography 2005; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United Kingdom
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; CRYSTALLIZATION; CRYSTALS; DIFFUSION; DISTRIBUTION; MATHEMATICAL SOLUTIONS; RESOLUTION; SOLUTIONS; SPACE GROUPS; X-RAY DIFFRACTION

Citation Formats

Zawacka, Anna, Loll, Bernhard, Biesiadka, Jacek, Saenger, Wolfram, Uchanska-Ziegler, Barbara, and Ziegler, Andreas, E-mail: andreas.ziegler@charite.de. X-ray diffraction analysis of crystals from the human major histocompatibility antigen HLA-B*2706 in complex with a viral peptide and with a self-peptide. United Kingdom: N. p., 2005. Web. doi:10.1107/S1744309105037966.
Zawacka, Anna, Loll, Bernhard, Biesiadka, Jacek, Saenger, Wolfram, Uchanska-Ziegler, Barbara, & Ziegler, Andreas, E-mail: andreas.ziegler@charite.de. X-ray diffraction analysis of crystals from the human major histocompatibility antigen HLA-B*2706 in complex with a viral peptide and with a self-peptide. United Kingdom. doi:10.1107/S1744309105037966.
Zawacka, Anna, Loll, Bernhard, Biesiadka, Jacek, Saenger, Wolfram, Uchanska-Ziegler, Barbara, and Ziegler, Andreas, E-mail: andreas.ziegler@charite.de. Thu . "X-ray diffraction analysis of crystals from the human major histocompatibility antigen HLA-B*2706 in complex with a viral peptide and with a self-peptide". United Kingdom. doi:10.1107/S1744309105037966.
@article{osti_22356206,
title = {X-ray diffraction analysis of crystals from the human major histocompatibility antigen HLA-B*2706 in complex with a viral peptide and with a self-peptide},
author = {Zawacka, Anna and Loll, Bernhard and Biesiadka, Jacek and Saenger, Wolfram and Uchanska-Ziegler, Barbara and Ziegler, Andreas, E-mail: andreas.ziegler@charite.de},
abstractNote = {The crystallization of HLA-B*2706 in complex with two peptides is reported. The human leukocyte antigen (HLA) alleles HLA-B*2704 and HLA-B*2706 show an ethnically restricted distribution and are differentially associated with ankylosing spondylitis, with HLA-B*2706 lacking association with this autoimmune disease. However, the products of the two alleles differ by only two amino acids, at heavy-chain residues 114 (His in HLA-B*2704; Asp in HLA-B*2706) and 116 (Asp in HLA-B*2704; Tyr in HLA-B*2706). Both residues could be involved in contacting amino acids of a bound peptide, suggesting that peptides presented by these subtypes play a role in disease pathogenesis. Two HLA-B*2706–peptide complexes were crystallized using the hanging-drop vapour-diffusion method with PEG as precipitant. Data sets were collected to resolutions of 2.70 Å (viral peptide pLMP2, RRRWRRLTV; space group P2{sub 1}2{sub 1}2{sub 1}) and 1.83 Å (self-peptide pVIPR, RRKWRRWHL; space group P2{sub 1}). Using HLA-B*2705 complexed with the pGR peptide (RRRWHRWRL) as a search model, unambiguous molecular-replacement solutions were found for both HLA-B*2706 complexes.},
doi = {10.1107/S1744309105037966},
journal = {Acta Crystallographica. Section F},
number = Pt 12,
volume = 61,
place = {United Kingdom},
year = {Thu Dec 01 00:00:00 EST 2005},
month = {Thu Dec 01 00:00:00 EST 2005}
}
  • Crystallization of HLA-B*2704 in complex with two peptides. The product of the human leukocyte antigen (HLA) gene HLA-B*2704 differs from that of the prototypical subtype HLA-B*2705 by three amino acids at heavy-chain residues 77 (Ser instead of Asp), 152 (Glu instead of Val) and 211 (Gly instead of Ala). In contrast to the ubiquitous HLA-B*2705 subtype, HLA-B*2704 occurs only in orientals. Both subtypes are strongly associated with spondyloarthropathies and the peptides presented by these subtypes are suspected to play a role in disease pathogenesis. HLA-B*2704 was crystallized in complex with a viral peptide and with a self-peptide using the hanging-dropmore » vapour-diffusion method with PEG as a precipitant. Both crystals belong to space group P2{sub 1}2{sub 1}2{sub 1}. Data sets were collected to 1.60 Å (complex with the self-peptide pVIPR) or to 1.90 Å (complex with the viral peptide pLMP2) resolution using synchrotron radiation. With HLA-B*2705 complexed with pVIPR as a search model, unambiguous molecular-replacement solutions were found for the complexes of HLA-B*2704 with both peptides.« less
  • The product of the human leukocyte antigen (HLA) gene HLA-B*2703 differs from that of the prototypical subtype HLA-B*2705 by a single amino acid at heavy-chain residue 59 that is involved in anchoring the peptide N-terminus within the A pocket of the molecule. Two B*2703–peptide complexes were crystallized using the hanging-drop vapour-diffusion method using PEG 8000 as a precipitant. A pocket of the molecule, two HLA-B*2703–peptide complexes were crystallized and data sets were collected to high resolution using synchrotron radiation. The product of the human leukocyte antigen (HLA) gene HLA-B*2703 differs from that of the prototypical subtype HLA-B*2705 by a singlemore » amino acid at heavy-chain residue 59 that is involved in anchoring the peptide N-terminus within the A pocket of the molecule. Two B*2703–peptide complexes were crystallized using the hanging-drop vapour-diffusion method using PEG 8000 as a precipitant. The crystals belong to space group P2{sub 1} (pVIPR peptide) or P2{sub 1}2{sub 1}2{sub 1} (pLMP2 peptide). Data sets were collected to 1.55 Å (B*2703–pVIPR) or 2.0 Å (B*2703–pLMP2) resolution using synchrotron radiation. With B*2705–pVIPR as a search model, a clear molecular-replacement solution was found for both B*2703 complexes.« less
  • The crystallization of HLA-B*1402 in complex with two peptides is reported. The product of the human major histocompatibility (HLA) class I allele HLA-B*1402 only differs from that of allele HLA-B*1403 at amino-acid position 156 of the heavy chain (Leu in HLA-B*1402 and Arg in HLA-B*1403). However, both subtypes are known to be differentially associated with the inflammatory rheumatic disease ankylosing spondylitis (AS) in black populations in Cameroon and Togo. HLA-B*1402 is not associated with AS, in contrast to HLA-B*1403, which is associated with this disease in the Togolese population. The products of these alleles can present peptides with Arg atmore » position 2, a feature shared by a small group of other HLA-B antigens, including HLA-B*2705, the prototypical AS-associated subtype. Complexes of HLA-B*1402 with a viral peptide (RRRWRRLTV, termed pLMP2) and a self-peptide (IRAAPPPLF, termed pCatA) were prepared and were crystallized using polyethylene glycol as precipitant. The complexes crystallized in space groups P2{sub 1} (pLMP2) and P2{sub 1}2{sub 1}2{sub 1} (pCatA) and diffracted synchrotron radiation to 2.55 and 1.86 Å resolution, respectively. Unambiguous solutions for both data sets were obtained by molecular replacement using a peptide-complexed HLA-B*2705 molecule (PDB code) as a search model.« less
  • A 600-kilobase (kb) DNA segment from the human major histocompatibility complex (MHC) class III region was isolated by extension of a previous 435-kb chromosome walk. The contiguous series of cloned overlapping cosmids contains the entire 555-kb interval between C2 in the complement gene cluster and HLA-B. This region is known to encode the tumor necrosis factors (TNFs) {alpha} and {beta}, B144, and the major heat shock protein HSP70. Moreover, a cluster of genes, BAT1-BAT5 (HLA-B-associated transcripts) have been localized in the vicinity of the genes for TNF{alpha} and TNF{beta}. An additional four genes were identified by isolation of corresponding cDNAmore » clones with cosmid DNA probes. These genes for BAT6-BAT9 were mapped near the gene for C2 within a 120-kb region that includes a HSP70 gene pair. These results, together with complementary data from a similar recent study, indicated the presence of a minimum of 19 genes within the C2-HLA-B interval of the MHC class III region. Although the functional properties of most of these genes are yet unknown, they may be involved in some aspects of immunity. This idea is supported by the genetic mapping of the hematopoietic histocompatibility locus-1 (Hh-1) in recombinant mice between TNF{alpha} and H-2S, which is homologous to the complement gene cluster in humans.« less