Structures of two major allergens, Bla g 4 and Per a 4, from cockroaches and their IgE binding epitopes.

Autor:	Tan YW; Department of Biological Sciences, National University of Singapore, Singapore 17543., Chan SL; Department of Biological Sciences, National University of Singapore, Singapore 17543., Ong TC; Department of Biological Sciences, National University of Singapore, Singapore 17543., Yit LY; Department of Biological Sciences, National University of Singapore, Singapore 17543., Tiong YS; Department of Biological Sciences, National University of Singapore, Singapore 17543., Chew FT; Department of Biological Sciences, National University of Singapore, Singapore 17543., Sivaraman J; Department of Biological Sciences, National University of Singapore, Singapore 17543. Electronic address: dbsjayar@dbs.nus.edu.sg., Mok YK; Department of Biological Sciences, National University of Singapore, Singapore 17543. Electronic address: dbsmokh@nus.edu.sg.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2009 Jan 30; Vol. 284 (5), pp. 3148-3157. Date of Electronic Publication: 2008 Dec 04.
DOI:	10.1074/jbc.M807209200
Abstrakt:	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.
Databáze:	MEDLINE
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