Crystal Structure of the Major Malassezia sympodialis Allergen Mala s 1 Reveals a β-Propeller Fold: A Novel Fold Among Allergens

Vilhelmsson, Monica; Zargari, Arezou; Crameri, Reto; Rasool, Omid; Achour, Adnane; Scheynius, Annika; Hällberg, B. Martin

doi:10.1016/j.jmb.2007.04.009

Cited by 25 publications

(23 citation statements)

References 44 publications

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“…Here we predicted four of the known allergens to be secreted proteins (Table 4). Combining this observation with proteomics experiments on the M. globosa orthologs (6) and results from a previous study that showed that Mala s 1 and 12 are expressed on the cell surface of Malassezia (36), we suggest that these allergens may be exported and/or loosely associated with the cell wall, for example, via disulfide bonds (27) or, for Mala s 1, via binding to phosphoinositides involved in membrane trafficking (34). Notably, the characterized ortholog of Mala s 1 from the wheat pathogen Fusarium graminearum (Tri 14) was proposed to be functionally associated (either as a regulator or as a transporter) with an adjacent gene cluster involved in biosynthesis of a mycotoxin (37).…”

Section: Resultssupporting

confidence: 71%

“…The 3-D structure indicates that Mala s 1 is a β-propeller-folded protein. This novel fold among allergens has structural similarity in the potential homologs Q4P4P8 and Tri 14, from the plant pathogens U. maydis and Gibberella zeae , respectively (34), suggesting that Mala s 1 and the plant pathogen proteins may have similar functions. Because gene deletion approaches have not been established for Malassezia , we investigated the role of the Mala s 1 ortholog in the related smut fungus U. maydis .…”

Section: Resultsmentioning

confidence: 99%

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Genomic Insights into the Atopic Eczema-Associated Skin Commensal Yeast Malassezia sympodialis

Gioti

Nystedt

et al. 2013

mBio

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Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of Malassezia globosa, associated with dandruff, as well as those of other closely related fungi. Ninety percent of the predicted M. sympodialis protein coding genes were experimentally verified by mass spectrometry at the protein level. We identified a relatively limited number of genes related to lipid biosynthesis, and both species lack the fatty acid synthase gene, in line with the known requirement of these yeasts to assimilate lipids from the host. Malassezia species do not appear to have many cell wall-localized glycosylphosphatidylinositol (GPI) proteins and lack other cell wall proteins previously identified in other fungi. This is surprising given that in other fungi these proteins have been shown to mediate interactions (e.g., adhesion and biofilm formation) with the host. The genome revealed a complex evolutionary history for an allergen of unknown function, Mala s 7, shown to be encoded by a member of an amplified gene family of secreted proteins. Based on genetic and biochemical studies with the basidiomycete human fungal pathogen Cryptococcus neoformans, we characterized the allergen Mala s 6 as the cytoplasmic cyclophilin A. We further present evidence that M. sympodialis may have the capacity to undergo sexual reproduction and present a model for a pseudobipolar mating system that allows limited recombination between two linked MAT loci.

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Section: Resultssupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Genomic Insights into the Atopic Eczema-Associated Skin Commensal Yeast Malassezia sympodialis

Gioti

Nystedt

et al. 2013

mBio

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111

211

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“…The complexity of the genus Malassezia is further highlighted by the structure of the major allergen of M. sympodialis, termed Mala s 1. This allergen has sequences that are found only in this particular species (109) and also demonstrates a crystallized 6-fold-␤-propeller structure, a novel fold among allergens (322).…”

Section: Atopic Eczemamentioning

confidence: 99%

The Malassezia Genus in Skin and Systemic Diseases

et al. 2012

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SUMMARY In the last 15 years, the genus Malassezia has been a topic of intense basic research on taxonomy, physiology, biochemistry, ecology, immunology, and metabolomics. Currently, the genus encompasses 14 species. The 1996 revision of the genus resulted in seven accepted taxa: M. furfur , M. pachydermatis , M. sympodialis , M. globosa , M. obtusa , M. restricta , and M. slooffiae. In the last decade, seven new taxa isolated from healthy and lesional human and animal skin have been accepted: M. dermatis , M. japonica , M. yamatoensis , M. nana , M. caprae , M. equina , and M. cuniculi. However, forthcoming multidisciplinary research is expected to show the etiopathological relationships between these new species and skin diseases. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. Their role in aggravating seborrheic dermatitis, dandruff, folliculitis, and onychomycosis, though often supported by histopathological evidence and favorable antifungal therapeutic outcomes, remains under investigation. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown, while laboratory data support a role in psoriasis exacerbations. Finally, metabolomic research resulted in the proposal of a hypothesis on the contribution of Malassezia -synthesized aryl hydrocarbon receptor (AhR) ligands to basal cell carcinoma through UV radiation-induced carcinogenesis.

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“…Although the clinical relevance of cross‐reactivity between fungal allergens remains to be investigated in more detail , the phenomenon is well understood at a scientific level. The availability of high‐resolution three‐dimensional structures of eight fungal allergens allowed researchers to understand in details the structural basis of cross‐reactivity , to homology model unsolved structures of fungal allergens and to test the correctness of the hypotheses by site‐directed mutagenesis and immunological investigations . Moreover, serologic studies involving recombinant A. fumigatus allergens contributed to corroborate a clinical diagnosis of ABPA by the discovery of disease‐specific allergens .…”

Section: Fungal Allergensmentioning

confidence: 99%

Fungi: the neglected allergenic sources

Crameri

Garbani

Rhyner

et al. 2013

Allergy

166

165

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Allergic diseases are considered the epidemics of the twentieth century estimated to affect more than 30% of the population in industrialized countries with a still increasing incidence. During the past two decades, the application of molecular biology allowed cloning, production and characterization of hundreds of recombinant allergens. In turn, knowledge about molecular, chemical and biologically relevant allergens contributed to increase our understanding of the mechanisms underlying IgE-mediated type I hypersensitivity reactions. It has been largely demonstrated that fungi are potent sources of allergenic molecules covering a vast variety of molecular structures including enzymes, toxins, cell wall components and phylogenetically highly conserved cross-reactive proteins. Despite the large knowledge accumulated and the compelling evidence for an involvement of fungal allergens in the pathophysiology of allergic diseases, fungi as a prominent source of allergens are still largely neglected in basic research as well as in clinical practice. This review aims to highlight the impact of fungal allergens with focus on asthma and atopic dermatitis.Allergy is a disease with many faces that can affect different organs like upper and lower respiratory tract, eyes, intestinal tract and the skin. Depending on the affected organ, allergic symptoms manifest as allergic rhinitis (1), allergic asthma (2), IgE-associated atopic dermatitis (3), food allergy (4) or insect venom allergy (5), to mention only the most important ones. The common hallmark of allergic diseases is a switch to the production of allergen-specific IgE raised against normally innocuous environmental allergens (6) that, in special cases, might also cross-react with self-antigens (7,8). At this asymptomatic stage, the individual is sensitized to a given allergenic source due to the presence of allergen-specific IgE in serum, a condition also called 'atopy'. Detection of allergen-specific IgE is considered as a specific biomarker for the atopic state in clinical practice, which allows in most cases a linkage of a symptom to a particular allergen exposure (9). Measurement of allergen-specific IgE antibodies in serum is normally performed with fully automated devices (10) and used to confirm sensitization to a particular allergen in support of a history-based clinical diagnosis of allergy or a symptom-based suspicion. In sensitized (atopic) individuals, however, re-exposure to the offending allergen induces crosslinking of the high-affinity receptor FceRI-bound allergenspecific IgE on effector cells and, thus, immediate release of anaphylactogenic mediators (11). Although the mechanisms leading to allergic reactions (12, 13) and the sources of exposure are quite well known, our knowledge about the repertoire of molecular structures involved in the pathogenesis of allergic reactions is still rudimentary (14) even if it is well recognized that only a minor fraction of the myriad of proteins to which humans are exposed provokes allergic reactions. Bioinfo...

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Crystal Structure of the Major Malassezia sympodialis Allergen Mala s 1 Reveals a β-Propeller Fold: A Novel Fold Among Allergens

Cited by 25 publications

References 44 publications

Genomic Insights into the Atopic Eczema-Associated Skin Commensal Yeast Malassezia sympodialis

Genomic Insights into the Atopic Eczema-Associated Skin Commensal Yeast Malassezia sympodialis

The Malassezia Genus in Skin and Systemic Diseases

Fungi: the neglected allergenic sources

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