THE 1.5 A CRYSTAL STRUCTURE OF THE MALASSEZIA SYMPODIALIS MALA S 6 ALLERGEN, A MEMBER OF THE CYCLOPHILIN PAN-ALLERGEN FAMILY

File:2cfe.gif


2cfe, resolution 1.50Å

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OverviewOverview

Cyclophilins constitute a family of proteins involved in many essential, cellular functions. They have also been identified as a panallergen family, able to elicit IgE-mediated hypersensitivity reactions. Moreover, it has, been shown that human cyclophilins are recognized by serum IgE from, patients sensitized to environmental cyclophilins. IgE-mediated, autoreactivity to self-antigens that have similarity to environmental, allergens is often observed in atopic disorders. Therefore comparison of, the crystal structure of human proteins with similarity to allergens, should allow the identification of structural similarities to rationally, explain autoreactivity. A new cyclophilin from Aspergillus fumigatus (Asp, f 27) has been cloned, expressed and showed to exhibit cross-reactivity in, vitro and in vivo. The three-dimensional structure of cyclophilin from the, yeast Malassezia sympodialis (Mala s 6) has been determined at 1.5 A (1, A=0.1 nm) by X-ray diffraction. Crystals belong to space group P4(1)2(1)2, with unit cell dimensions of a=b=71.99 A and c=106.18 A. The structure was, solved by molecular replacement using the structure of human cyclophilin A, as the search model. The refined structure includes all 162 amino acids of, Mala s 6, an active-site-bound Ala-Pro dipeptide and 173 water molecules, with a crystallographic R- and free R-factor of 14.3% and 14.9%, respectively. The overall structure consists of an eight-stranded, antiparallel beta-barrel and two alpha-helices covering the top and bottom, of the barrel, typical for cyclophilins. We identified conserved, solvent-exposed residues in the fungal and human structures that are, potentially involved in the IgE-mediated cross-reactivity.

About this StructureAbout this Structure

2CFE is a Single protein structure of sequence from Malassezia sympodialis with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Analysis of the cross-reactivity and of the 1.5 A crystal structure of the Malassezia sympodialis Mala s 6 allergen, a member of the cyclophilin pan-allergen family., Glaser AG, Limacher A, Fluckiger S, Scheynius A, Scapozza L, Crameri R, Biochem J. 2006 May 15;396(1):41-9. PMID:16483252

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