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Publication Abstract from PubMed

BACKGROUND: Alternaria species is one of the most common molds associated with allergic diseases, and 80% of Alternaria species-sensitive patients produce IgE antibodies to a major protein allergen, Alt a 1. The structure and function of Alt a 1 is unknown. OBJECTIVE: We sought to obtain a high-resolution structure of Alt a 1 using x-ray crystallography and to investigate structural relationships between Alt a 1 and other allergens and proteins reported in the Protein Data Bank. METHODS: X-ray crystallography was used to determine the structure of Alt a 1 by using a custom-designed set of crystallization conditions. An initial Alt a 1 model was determined by the application of a Ta(6)Br(12)(2+) cluster and single-wavelength anomalous diffraction. Bioinformatic analyses were used to compare the Alt a 1 sequence and structure with that of other proteins. RESULTS: Alt a 1 is a unique beta-barrel comprising 11 beta-strands and forms a "butterfly-like" dimer linked by a single disulfide bond with a large (1345 A(2)) dimer interface. Intramolecular disulfide bonds are conserved among Alt a 1 homologs. Currently, the Alt a 1 structure has no equivalent in the Protein Data Bank. Bioinformatics analyses suggest that the structure is found exclusively in fungi. Four previously reported putative IgE-binding peptides have been located on the Alt a 1 structure. CONCLUSIONS: Alt a 1 has a unique, dimeric beta-barrel structure that appears to define a new protein family with unknown function found exclusively in fungi. The location of IgE antibody-binding epitopes is in agreement with the structural analysis of Alt a 1. The Alt a 1 structure will allow mechanistic structure/function studies and immunologic studies directed toward new forms of immunotherapy for Alternaria species-sensitive allergic patients.

Alternaria alternata allergen Alt a 1: A unique beta-barrel protein dimer found exclusively in fungi.,Chruszcz M, Chapman MD, Osinski T, Solberg R, Demas M, Porebski PJ, Majorek KA, Pomes A, Minor W J Allergy Clin Immunol. 2012 Jun 2. PMID:22664167^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.