Structures of two major allergens, Bla g 4 and Per a 4, from cockroaches and their IgE binding epitopes.
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.
Tan
Yih Wan
YW
Department of Biological Sciences, National University of Singapore, Singapore 17543.
Chan
Siew Leong
SL
Department of Biological Sciences, National University of Singapore, Singapore 17543.
Ong
Tan Ching
TC
Department of Biological Sciences, National University of Singapore, Singapore 17543.
Yit
Le Yau
LY
Department of Biological Sciences, National University of Singapore, Singapore 17543.
Tiong
Yuen Sung
YS
Department of Biological Sciences, National University of Singapore, Singapore 17543.
Chew
Fook Tim
FT
Department of Biological Sciences, National University of Singapore, Singapore 17543.
Sivaraman
J
J
Department of Biological Sciences, National University of Singapore, Singapore 17543. Electronic address: dbsjayar@dbs.nus.edu.sg.
Mok
Yu Keung
YK
Department of Biological Sciences, National University of Singapore, Singapore 17543. Electronic address: dbsmokh@nus.edu.sg.
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
D000485:Allergens; D052179:Antigens, Plant; C097505:Blatella germanica allergen 4; D000939:Epitopes; D019476:Insect Proteins; D008024:Ligands; D007073:Immunoglobulin E