Dataset Information

Structure and function of a fungal adhesin that binds heparin and mimics thrombospondin-1 by blocking T cell activation and effector function.

ABSTRACT: Blastomyces adhesin-1 (BAD-1) is a 120-kD surface protein on B. dermatitidis yeast. We show here that BAD-1 contains 41 tandem repeats and that deleting even half of them impairs fungal pathogenicity. According to NMR, the repeats form tightly folded 17-amino acid loops constrained by a disulfide bond linking conserved cysteines. Each loop contains a highly conserved WxxWxxW motif found in thrombospondin-1 (TSP-1) type 1 heparin-binding repeats. BAD-1 binds heparin specifically and saturably, and is competitively inhibited by soluble heparin, but not related glycosaminoglycans. According to SPR analysis, the affinity of BAD-1 for heparin is 33 nM±14 nM. Putative heparin-binding motifs are found both at the N-terminus and within each tandem repeat loop. Like TSP-1, BAD-1 blocks activation of T cells in a manner requiring the heparan sulfate-modified surface molecule CD47, and impairs effector functions. The tandem repeats of BAD-1 thus confer pathogenicity, harbor motifs that bind heparin, and suppress T-cell activation via a CD47-dependent mechanism, mimicking mammalian TSP-1.

SUBMITTER: Brandhorst TT

PROVIDER: S-EPMC3708853 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Publications

Structure and function of a fungal adhesin that binds heparin and mimics thrombospondin-1 by blocking T cell activation and effector function.

Brandhorst T Tristan TT Roy René R Wüthrich Marcel M Nanjappa Som S Filutowicz Hanna H Galles Kevin K Tonelli Marco M McCaslin Darrell R DR Satyshur Kenneth K Klein Bruce B

PLoS pathogens 20130711 7

Blastomyces adhesin-1 (BAD-1) is a 120-kD surface protein on B. dermatitidis yeast. We show here that BAD-1 contains 41 tandem repeats and that deleting even half of them impairs fungal pathogenicity. According to NMR, the repeats form tightly folded 17-amino acid loops constrained by a disulfide bond linking conserved cysteines. Each loop contains a highly conserved WxxWxxW motif found in thrombospondin-1 (TSP-1) type 1 heparin-binding repeats. BAD-1 binds heparin specifically and saturably, an ...[more]

PMID: 23853587

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Project description:Effector proteins are secreted by plant pathogens to enable host colonization. Typically, effector genes are tightly regulated, have very low expression levels in axenic conditions, and are strongly induced during host colonization. Chromatin remodeling contributes to the activation of effector genes in planta by still poorly known mechanisms. In this work, we investigated the role of histone acetylation in effector gene derepression in plant pathogens. We used Zymoseptoria tritici, a major pathogen of wheat, as a model to determine the role of lysine acetyltransferases (KATs) in plant infection. We showed that effector gene activation is associated with chromatin remodeling, featuring increased acetylation levels of histone H3 lysine 9 (H3K9) and 14 (H3K14) in effector loci. We functionally characterized the role of Z. tritici KATs and demonstrated their distinct contributions to growth, development, and infection. Sas3 is required for host colonization and pycnidia production and is involved in the acetylation of H3K9 and H3K14 in effector loci and, consequently, in effector gene activation during plant infection. We propose that Sas3-mediated histone acetylation is required for the spatiotemporal activation of effector genes and the virulence of Z. tritici. IMPORTANCE Pathogen infections require the production of effectors that enable host colonization. Effectors have diverse functions and are only expressed at certain stages of the infection cycle. Thus, effector genes are tightly regulated by several mechanisms, including chromatin remodeling. Here, we investigate the role of histone acetylation in effector gene activation in the fungal wheat pathogen Zymoseptoria tritici. We demonstrate that lysine acetyltransferases (KATs) are essential for the spatiotemporal regulation of effector genes. We show that the KAT Sas3 is involved in leaf symptom development and pycnidia formation. Importantly, our results indicate that Sas3 controls histone acetylation of effector loci and is a regulator of effector gene activation during stomatal penetration. Overall, our work demonstrates the key role of histone acetylation in regulating gene expression associated with plant infection.

Dataset Information

Structure and function of a fungal adhesin that binds heparin and mimics thrombospondin-1 by blocking T cell activation and effector function.

Publications

Structure and function of a fungal adhesin that binds heparin and mimics thrombospondin-1 by blocking T cell activation and effector function.

Similar Datasets

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