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

一组叫做G蛋白偶联受体（gpcr）的普通细胞表面受体的一些成员可以被几个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，或者受体是否无法区分它们。迄今为止的证据表明，激活剂的细微差异实际上可以被这些受体检测到。本项目将探讨受体如何识别它们的多个激活剂。从裂叶菌（Schizophyllum commune）中提取的一组gpcr及其信息素激活剂将作为实验模型。受体和信息素将发生微小的、离散的变化，以确定这些分子内的区域，这些区域对确定它们的相互和特定识别很重要。从研究这些受体和信息素中获得的新信息将对理解其他生物体中相同类型的受体具有重要意义，在这些生物体中，对其中一个或另一个伙伴知之甚少。受体和信息素都将使用分子遗传技术进行研究，重点是重组DNA技术。另一种遗传模型真菌——面包酵母（Saccharomyces cerevisiae）将被用作替代生物，用于测试蘑菇受体和信息素的变化，因为这种酵母可以以很高的效率生长和操纵。这项基础生物学研究的潜在影响是巨大的。S. commune利用它的受体和信息素来识别合适的交配对象，而同样复杂的受体和激活剂是动物和人类味觉和嗅觉的基础，此外，一些动物的交配行为也是如此。很大比例的药物靶向gpcr，因此更好地了解gpcr的功能将有助于理解药物的作用和设计。目前正在提交给堪萨斯大学真菌遗传资源中心的S. commune收集将为进一步研究这些受体和信息素提供遗传资源。此外，本项目将为本科生提供在现代遗传学、分子遗传学和微生物学方面的实践训练机会。

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.