Phylogenetic and preliminary phenotypic analysis of yeast PAQR receptors: potential antifungal targets.
Phylogenetic and preliminary phenotypic analysis of yeast PAQR receptors: potential antifungal targets.
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DOI：
10.1007/s00239-011-9462-3
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发表时间：
2011-10
影响因子：
3.9
通讯作者：
Lyons, Thomas J.
中科院分区：
文献类型：
--
作者：
Villa, Nancy Y.;Moussatche, Patricia;Chamberlin, Stephen G.;Kumar, Anuj;Lyons, Thomas J.
关键词：
属于膜结合受体的孕激素和AdipoQ受体（PAQR）超家族的蛋白质在真菌中普遍存在。几乎所有真菌都具有两种进化上截然不同的PAQR蛋白，我们称之为PQRA和PQRB亚型。在模式真菌酿酒酵母中，这些亚型分别由Izh2p和Izh3p蛋白代表。酿酒酵母还拥有两个额外的pqra型受体，称为Izh1p和Izh4p，这些受体仅限于“Saccharomyces complex”中的其他物种。Izh2p已成为最近几项研究的主题，并且特别令人感兴趣，因为它调节真菌对植物产生的蛋白质的生长，因此代表了种间交流的新范式。结果表明，IZH2和IZH3基因剂量影响对多烯类抗真菌药物的耐药性。此外，我们提供了额外的证据，证明Izh2p和Izh3p负调控真菌的丝化。这些数据表明，这些受体的激动剂可能通过抑制真菌发育或使真菌对当前抗真菌治疗的毒性作用敏感而成为抗真菌治疗药物。这对于与酿酒酵母密切相关且含有相同PAQR受体补体的光假丝酵母（Candida glabrata）等致病真菌尤其重要。本文的在线版本（doi:10.1007/s00239-011-9462-3）包含补充材料，授权用户可使用。
Proteins belonging to the Progestin and AdipoQ Receptor (PAQR) superfamily of membrane bound receptors are ubiquitously found in fungi. Nearly, all fungi possess two evolutionarily distinct paralogs of PAQR protein, which we have called the PQRA and PQRB subtypes. In the model fungus Saccharomyces cerevisiae, these subtypes are represented by the Izh2p and Izh3p proteins, respectively. S. cerevisiae also possesses two additional PQRA-type receptors called Izh1p and Izh4p that are restricted to other species within the “Saccharomyces complex”. Izh2p has been the subject of several recent investigations and is of particular interest because it regulates fungal growth in response to proteins produced by plants and, as such, represents a new paradigm for interspecies communication. We demonstrate that IZH2 and IZH3 gene dosage affects resistance to polyene antifungal drugs. Moreover, we provide additional evidence that Izh2p and Izh3p negatively regulate fungal filamentation. These data suggest that agonists of these receptors might make antifungal therapeutics, either by inhibiting fungal development or by sensitizing fungi to the toxic effects of current antifungal therapies. This is particularly relevant for pathogenic fungi such as Candida glabrata that are closely related to S. cerevisiae and contain the same complement of PAQR receptors. The online version of this article (doi:10.1007/s00239-011-9462-3) contains supplementary material, which is available to authorized users.
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