Alternaria alternata allergen Alt a 1: a unique β-barrel protein dimer found exclusively in fungi.
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.
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA. maks@iwonka.med.virginia.edu
Maksymilian
M
Chruszcz
Martin D
MD
Chapman
Tomasz
T
Osinski
Robert
R
Solberg
Matthew
M
Demas
Przemyslaw J
PJ
Porebski
Karolina A
KA
Majorek
Anna
A
Pomés
Wladek
W
Minor
D000328:Adult; D000485:Allergens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000528:Alternaria / Q000276:immunology / Q000378:metabolism*; D000595:Amino Acid Sequence; D002648:Child; D019295:Computational Biology; D018360:Crystallography, X-Ray; D019281:Dimerization; D000939:Epitopes; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D008958:Models, Molecular; D016415:Sequence Alignment
C096258:ALTA1 protein, Alternaria alternata; D000485:Allergens; D000939:Epitopes; D005656:Fungal Proteins; D007073:Immunoglobulin E