title: Structures of two major allergens, Bla g 4 and Per a 4, from cockroaches and their IgE binding epitopes.
abstract: Inhalant allergens from cockroaches are an important cause of asthma to millions of individuals worldwide. Here we report for the first time the structures of two major cockroach allergens, Bla g 4 and Per a 4, that adopt a typical lipocalin fold but with distinct structural features as compared with other known lipocalin allergens. Both Bla g 4 and Per a 4 contain two long-range disulfide bonds linking the N and C termini to a beta-barrel. The C-terminal helix of Bla g 4 is bent and greatly extended toward the N terminus. Bla g 4 is found to be a monomer, whereas Per a 4 exists as a dimer in solution with a novel dimeric interface involving residues from loops at the top and bottom of the beta-barrel. Putative ligand binding sites of both allergens are determined by docking of the juvenile hormone III inside the beta-barrel and found to interact with the ligand using non-conserved residues. Bla g 4 and Per a 4 are found to be cross-reactive in sera IgE binding, at least in the Singaporean Chinese population tested. A major IgE binding epitope unique to Per a 4 is found on the loops at the bottom of the beta-barrel that may aid the development of hypoallergens for immunotherapy.
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 17543.
authors.forename: Yih Wan
authors.initials: YW
authors.lastname: Tan
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 17543.
authors.forename: Siew Leong
authors.initials: SL
authors.lastname: Chan
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 17543.
authors.forename: Tan Ching
authors.initials: TC
authors.lastname: Ong
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 17543.
authors.forename: Le Yau
authors.initials: LY
authors.lastname: Yit
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 17543.
authors.forename: Yuen Sung
authors.initials: YS
authors.lastname: Tiong
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 17543.
authors.forename: Fook Tim
authors.initials: FT
authors.lastname: Chew
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 17543. Electronic address: dbsjayar@dbs.nus.edu.sg.
authors.forename: J
authors.initials: J
authors.lastname: Sivaraman
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 17543. Electronic address: dbsmokh@nus.edu.sg.
authors.forename: Yu Keung
authors.initials: YK
authors.lastname: Mok
mesh_terms: D000485:Allergens / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D052179:Antigens, Plant; D001665:Binding Sites; D003058:Cockroaches / Q000276:immunology*; D003460:Crystallization; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D007073:Immunoglobulin E / Q000737:chemistry / Q000276:immunology*; D019476:Insect Proteins / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D000485:Allergens; D052179:Antigens, Plant; C097505:Blatella germanica allergen 4; D000939:Epitopes; D019476:Insect Proteins; D008024:Ligands; D007073:Immunoglobulin E