2j23

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(New page: 200px<br /><applet load="2j23" size="350" color="white" frame="true" align="right" spinBox="true" caption="2j23, resolution 1.41&Aring;" /> '''CROSS-REACTIVITY AND...)
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==Overview==
==Overview==
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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.
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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.
==About this Structure==
==About this Structure==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Crameri, R.]]
[[Category: Crameri, R.]]
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[[Category: Glaser, A.G.]]
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[[Category: Glaser, A G.]]
[[Category: Limacher, A.]]
[[Category: Limacher, A.]]
[[Category: Meier, C.]]
[[Category: Meier, C.]]
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[[Category: thioredoxin]]
[[Category: thioredoxin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 20:50:03 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:58:31 2008''

Revision as of 15:58, 21 February 2008


2j23, resolution 1.41Å

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CROSS-REACTIVITY AND CRYSTAL STRUCTURE OF MALASSEZIA SYMPODIALIS THIOREDOXIN (MALA S 13), A MEMBER OF A NEW PAN-ALLERGEN FAMILY

Overview

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.

About this Structure

2J23 is a Single protein structure of sequence from Malassezia sympodialis. Full crystallographic information is available from OCA.

Reference

Cross-reactivity and 1.4-A crystal structure of Malassezia sympodialis thioredoxin (Mala s 13), a member of a new pan-allergen family., Limacher A, Glaser AG, Meier C, Schmid-Grendelmeier P, Zeller S, Scapozza L, Crameri R, J Immunol. 2007 Jan 1;178(1):389-96. PMID:17182577

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