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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / chemistry*
  • Allergens / genetics
  • Allergens / immunology
  • Allergens / metabolism
  • Alternaria / immunology
  • Alternaria / metabolism*
  • Amino Acid Sequence
  • Child
  • Computational Biology
  • Crystallography, X-Ray
  • Dimerization
  • Epitopes
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics
  • Fungal Proteins / immunology
  • Fungal Proteins / metabolism
  • Humans
  • Immunoglobulin E / metabolism
  • Models, Molecular
  • Sequence Alignment


  • ALTA1 protein, Alternaria alternata
  • Allergens
  • Epitopes
  • Fungal Proteins
  • Immunoglobulin E

Associated data

  • PDB/3VOR