2J23

Cross-reactivity and crystal structure of Malassezia sympodialis Thioredoxin (Mala s 13), a member of a new pan-allergen family

Summary for 2J23

• Entry DOI: 10.2210/pdb2j23/pdb
• Descriptor: THIOREDOXIN (2 entities in total)
• Functional Keywords: malassezia sympodialis, immune protein, autoreactivity, cross-reactivity, ige, fungi, epitope, allergen, thioredoxin
• Biological source: MALASSEZIA SYMPODIALIS
• Total number of polymer chains: 2
• Total formula weight: 26678.32

Authors

Limacher, A.,Glaser, A.G.,Meier, C.,Scapozza, L.,Crameri, R. (deposition date: 2006-08-16, release date: 2006-11-22, Last modification date: 2024-10-16)

Primary citation

Limacher, A.,Glaser, A.G.,Meier, C.,Schmid-Grendelmeier, P.,Zeller, S.,Scapozza, L.,Crameri, R.
Cross-reactivity and 1.4-A crystal structure of Malassezia sympodialis thioredoxin (Mala s 13), a member of a new pan-allergen family.
J Immunol., 178:389-396, 2007

PubMed Abstract: We have identified thioredoxins (Trx) of Malassezia sympodialis, a yeast involved in the pathogenesis of atopic eczema, and of Aspergillus fumigatus, a fungus involved in pulmonary complications, as novel IgE-binding proteins. We show that these Trx, including the human enzyme, represent cross-reactive structures recognized by serum IgE from individuals sensitized to M. sympodialis Trx. Moreover, all three proteins were able to elicit immediate-type allergic skin reactions in sensitized individuals, indicating a humoral immune response based on molecular mimicry. To analyze structural elements involved in these reactions, the three-dimensional structure of M. sympodialis Trx (Mala s 13) has been determined at 1.4-A resolution by x-ray diffraction analysis. The structure was solved by molecular replacement and refined to a crystallographic R factor of 14.0% and a free R factor of 16.8% and shows the typical Trx fold. Mala s 13 shares 45% sequence identity with human Trx and superposition of the solved Mala s 13 structure with those of human Trx reveals a high similarity with a root mean square deviation of 1.11 A for all Calpha atoms. In a detailed analysis of the molecular surface in combination with sequence alignment, we identified conserved solvent-exposed amino acids scattered over the surface in both structures which cluster to patches, thus forming putative conformational B cell epitopes potentially involved in IgE-mediated cross- and autoreactivity.

PubMed: 17182577
DOI: 10.4049/jimmunol.178.1.389

Experimental method

X-RAY DIFFRACTION (1.41 Å)