Determinants of Molecular Recognition Between Pheromone Receptors and Lipopeptide Pheromones of Schizophyllum Commune

裂褶菌信息素受体与脂肽信息素分子识别的决定因素

• 批准号: 0237129
• 负责人: Thomas Fowler
• 金额: $ 30万
• 依托单位: University of Vermont & State Agricultural College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0237129&HistoricalAwards=false
• 关键词: Determinants; Molecular; Recognition; Between; Pheromone

Some members of a group of common cell surface receptors called the G protein coupled receptors, or GPCRs, can be stimulated by several activating molecules that appear dissimilar. It is not understood how a single receptor recognizes several seemingly different activators, or if the receptor simply cannot differentiate between them. Evidence to date suggests that subtle differences in activators can, in fact, be detected by these receptors. This project will explore how the receptors recognize their multiple activators. A set of GPCRs and their pheromone activators, derived from the mushroom fungus Schizophyllum commune, will be used as an experimental model. Small, discrete changes will be made in the receptors and pheromones in order to identify areas within these molecules that are important for determining their mutual and specific recognition. New information gained from studying these receptors and pheromones will have implications for understanding the same type of receptors in other organisms, where less is known about one or the other partner. Both receptors and pheromones will be studied using molecular genetic techniques with an emphasis on recombinant DNA technology. Another genetic model fungus, the baker's yeast Saccharomyces cerevisiae, will be employed as a surrogate organism in which to test the changes made in the mushroom's receptors and pheromones because this yeast can be grown and manipulated with great efficiency.The impact of this basic biological research is potentially great. S. commune uses its receptors and pheromones to recognize compatible mating partners, while similarly complex sets of receptors and activators are the basis of taste and smell in animals and humans and, additionally, mating behavior in some animals. A large percentage of pharmaceuticals target GPCRs, thus a better general understanding of how GPCRs function will be of benefit for understanding drug action and design. An S. commune collection currently being submitted to the Fungal Genetic Stock Center at Kansas University will provide a genetic resource for further studies on these receptors and pheromones. In addition, this project will provide opportunities for undergraduate students to receive hands-on training in modern genetics, molecular genetics, and microbiology.

称为 G 蛋白偶联受体 (GPCR) 的一组常见细胞表面受体的某些成员可以被几种看起来不同的激活分子刺激。 目前尚不清楚单个受体如何识别几种看似不同的激活剂，或者该受体是否根本无法区分它们。 迄今为止的证据表明，事实上，这些受体可以检测到激活剂的细微差异。 该项目将探索受体如何识别其多种激活剂。 一组源自蘑菇真菌裂褶菌的 GPCR 及其信息素激活剂将被用作实验模型。 将在受体和信息素中进行小的、离散的变化，以便识别这些分子内对于确定它们的相互和特异性识别很重要的区域。 通过研究这些受体和信息素获得的新信息将对理解其他生物体中的相同类型的受体产生影响，因为人们对其中一个或另一个伙伴知之甚少。 受体和信息素都将利用分子遗传学技术进行研究，重点是重组 DNA 技术。 另一种基因模型真菌，即面包酵母酿酒酵母，将被用作替代生物体，用于测试蘑菇受体和信息素的变化，因为这种酵母可以高效地生长和操纵。这项基础生物学研究的影响潜力巨大。 S. commune 使用其受体和信息素来识别兼容的交配伙伴，而类似的复杂受体和激活剂组是动物和人类味觉和嗅觉以及某些动物交配行为的基础。 很大一部分药物以 GPCR 为靶点，因此更好地了解 GPCR 的功能将有助于理解药物作用和设计。 目前正在提交给堪萨斯大学真菌遗传库存中心的 S. commune 收藏品将为进一步研究这些受体和信息素提供遗传资源。 此外，该项目将为本科生提供接受现代遗传学、分子遗传学和微生物学实践培训的机会。