Alternaria alternata allergen Alt a 1: a unique ?-barrel protein dimer found exclusively in fungi.

ABSTRACT:

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 ?-barrel comprising 11 ?-strands and forms a "butterfly-like" dimer linked by a single disulfide bond with a large (1345 Å(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 ?-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.

SUBMITTER: Chruszcz M 

PROVIDER: S-EPMC3391610 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature