title: Thermodynamic and structural analysis of peptide- and allele-dependent properties of two HLA-B27 subtypes exhibiting differential disease association.
abstract: Selected HLA-B27 subtypes are associated with spondyloarthropathies, but the underlying mechanism is not understood. To explain this association in molecular terms, a comparison of peptide-dependent dynamic and structural properties of the differentially disease-associated subtypes HLA-B*2705 and HLA-B*2709 was carried out. These molecules differ only by a single amino acid at the floor of the peptide binding groove. The thermostabilities of a series of HLA-B27 molecules complexed with nonameric and decameric peptides were determined and revealed substantial differences depending on the subtype as well as the residues at the termini of the peptides. In addition we present the crystal structure of the B*2709 subtype complexed with a decameric peptide. This structure provides an explanation for the preference of HLA-B27 for a peptide with an N-terminal arginine as secondary anchor and the lack of preference for tyrosine as peptide C terminus in B*2709. The data show that differences in thermodynamic properties between peptide-complexed HLA-B27 subtypes are correlated with a variety of structural properties.
authors.affiliation: Institut für Immungenetik, Charité, Humboldt-Universität zu Berlin, Spandauer Damm 130, 14050 Berlin, Germany.
authors.forename: Roman C
authors.initials: RC
authors.lastname: Hillig
authors.forename: Martin
authors.initials: M
authors.lastname: Hülsmeyer
authors.forename: Wolfram
authors.initials: W
authors.lastname: Saenger
authors.forename: Karin
authors.initials: K
authors.lastname: Welfle
authors.forename: Rolf
authors.initials: R
authors.lastname: Misselwitz
authors.forename: Heinz
authors.initials: H
authors.lastname: Welfle
authors.forename: Christine
authors.initials: C
authors.lastname: Kozerski
authors.forename: Armin
authors.initials: A
authors.lastname: Volz
authors.forename: Barbara
authors.initials: B
authors.lastname: Uchanska-Ziegler
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000276:immunology; D015796:HLA-B27 Antigen / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D015796:HLA-B27 Antigen; D010446:Peptide Fragments