title: Structural and computational investigations of the conformation of antigenic peptide fragments of human polymorphic epithelial mucin.
abstract: Human polymorphic epithelial mucins (PEM) are complex glycoproteins that are associated with breast and ovarian carcinomas. The PEM core protein consists of variable numbers of a tandem repeat sequence which contains a short antigenic hydrophilic region (Pro1-Asp-Thr-Arg-Pro-Ala-Pro7). High-field n.m.r. studies undertaken on antigenic 20- and 11-amino acid fragments of the PEM core protein in dimethyl sulphoxide have identified a type-I beta-turn to be present in the region Pro1-Asp-Thr-Arg4. This region includes and overlaps the identified type-I (Asp2-Thr-Arg4) and type-II (Arg4-Pro-Ala6) epitopes of anti-PEM monoclonal antibodies. The studies indicate that the beta-turn is stabilized by the presence of a salt-bridge interaction between Asp-2 and Arg-4. In order to probe the conformations accessible to the PEM peptides a computational study was undertaken independently on the peptide Pro-Asp-Thr-Arg-Pro using a modified Metropolis Monte Carlo algorithm. This study identified the n.m.r.-observed salt-bridge type-I beta-turn as the major low-energy conformer. These results suggest that this structural motif may be involved in the immune recognition of PEM.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nottingham, U.K.
authors.forename: M J
authors.initials: MJ
authors.lastname: Scanlon
authors.forename: S D
authors.initials: SD
authors.lastname: Morley
authors.forename: D E
authors.initials: DE
authors.lastname: Jackson
authors.forename: M R
authors.initials: MR
authors.lastname: Price
authors.forename: S J
authors.initials: SJ
authors.lastname: Tendler
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D000939:Epitopes / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D008956:Models, Chemical; D008969:Molecular Sequence Data; D018396:Mucin-1; D009077:Mucins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D000939:Epitopes; D008562:Membrane Glycoproteins; D018396:Mucin-1; D009077:Mucins; D010446:Peptide Fragments