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J Allergy Clin Immunol. 2012 Jul;130(1):241-7.e9. doi: 10.1016/j.jaci.2012.03.047. Epub 2012 Jun 2.

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

Author information

  • 1Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA. maks@iwonka.med.virginia.edu

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 β-barrel comprising 11 β-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 β-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.

Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

PMID:
22664167
[PubMed - indexed for MEDLINE]
PMCID:
PMC3391610
Free PMC Article

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