Analysis of the structure function and regulation of the Rho1-specific GTP-exchange proteins of the yeast cell wall integrity pathway

酵母细胞壁完整性途径Rho1特异性GTP交换蛋白的结构功能和调控分析

• 批准号: BB/E011632/1
• 负责人: Joseph Gray
• 金额: $ 48.31万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE011632%2F1
• 关键词: Analysis; structure; function; regulation; Rho1

The cells that make up every organism are delicate and intricate machines that must carry out many complex tasks to stay alive. The single celled fungus, the budding yeast, although modest in size, shares with our cells many of these intricate mechanisms. Yeast has the huge advantage over humans in scientific research: it is relatively easy and cheap to study. Many of the insights gained into how yeast cells work apply, in one form or another, to other organisms, including ourselves. Among the key tasks shared between yeast and human cells is the ability to grow bigger without bursting. Another is to survive changes in the immediate environment that threaten lysis (bursting), such as changes in temperature or nasty chemicals. Yeast possesses one main system that senses a variety of threats to the cell's integrity and responds so as to maintain that integrity (and thereby keep the cell alive) - the cell wall integrity (CWI) pathway. Many of the components of this system are shared with humans but some are not - these latter may be a fungus' Achilles' heel, to which drugs could be developed that cause fungal cells (many pathogenic) to blow up (die) leaving human cells undisturbed. The CWI pathway is worth understanding. In addition, the CWI pathway presents scientific puzzles that challenge our understanding of how living systems work. Multiple signals feed into this pathway, and the pathway can activate a variety of distinct responses: how can one pathway integrate many inputs and 'decide' to make a sensible response? Key regulators of the CWI pathway are proteins called GEFs. CWI-GEFs appear to come in two distinct flavours that appear to perform distinct roles in activating the pathway. In this proposal, we seek to better understand how these GEFs are regulated, how they differ from each other both structurally and functionally and how information is processed by these GEFs to affect CWI outputs in the appropriate way. We hope to better understand how the complex and important CWI pathway is regulated.

构成每个生物体的细胞都是精密而复杂的机器，必须执行许多复杂的任务才能存活。单细胞真菌，出芽酵母，虽然体积不大，但与我们的细胞共享许多复杂的机制。酵母在科学研究中比人类有巨大的优势：研究它相对容易和便宜。许多关于酵母细胞如何工作的见解，以一种或另一种形式，适用于其他生物，包括我们自己。酵母和人类细胞共有的关键任务之一是能够长得更大而不会破裂。另一个是在直接环境的变化中生存下来，这些变化可能会导致裂解（破裂），比如温度的变化或有害的化学物质。酵母有一个主要的系统，可以感知各种对细胞完整性的威胁，并做出反应，以维持这种完整性（从而保持细胞存活）——细胞壁完整性（CWI）途径。该系统的许多组成部分与人类共享，但有些则不是——后者可能是真菌的“阿喀琉斯之踵”，可以开发药物，使真菌细胞（许多致病细胞）爆炸（死亡），而不受人类细胞的干扰。CWI的路径值得理解。此外，CWI通路提出了挑战我们对生命系统如何工作的理解的科学难题。多种信号输入到这条通路，这条通路可以激活各种不同的反应：一条通路如何整合许多输入并“决定”做出明智的反应？CWI通路的关键调节因子是一种叫做gef的蛋白质。cwi - gef似乎有两种不同的口味，在激活该途径中似乎发挥着不同的作用。在本提案中，我们试图更好地了解这些gef是如何被调节的，它们在结构和功能上如何相互区别，以及这些gef如何处理信息以适当的方式影响CWI输出。我们希望更好地了解复杂而重要的CWI通路是如何调控的。