A Novel Class of Signal Transduction System in Streptococcus mutans

描述（由申请人提供）：拟议研究的目标是研究LytTR调节系统（LRS）用于控制基因表达的功能机制，并探索其在控制变形链球菌细胞死亡途径中的作用。LRS是一类新型的信号转导系统，其由LytTR家族转录调节因子和拮抗该调节因子功能的推定的膜蛋白抑制剂组成。本项目的目标将通过以下两个目标实现：1）确定LRS两种亚型所采用的抑制控制机制和2）确定LRS细胞死亡途径中的分级转录控制机制。1)为了确定LRS膜蛋白如何作为其同源转录调节蛋白的抑制剂发挥作用，我们将研究各种潜在的翻译后抑制控制机制，并绘制LRS蛋白中负责介导抑制的关键残基。蛋白质-蛋白质相互作用研究将确定LRS膜蛋白是否直接发挥其功能。2)为了确定HdrRM和BrsRM LRS的同时激活如何触发细胞死亡途径，我们将测试LRS之间正反馈交叉调节模型的关键方面。启动子结合研究将与转录输出响应相关。

DESCRIPTION (provided by applicant): The goals of the proposed research are to investigate the functional mechanism used by LytTR Regulatory Systems (LRS) to control gene expression and to explore their role in controlling a cell death pathway in Streptococcus mutans. LRS are a novel class of signal transduction system that consists of a LytTR family transcription regulator and putative membrane protein inhibitor that antagonizes the function of this regulator. The goals of this project will be achieved in two aims by: 1) determining the inhibitory control mechanism employed by two subtypes of LRS and 2) determining the hierarchical transcription control mechanism in the LRS cell death pathway. 1) To determine how LRS membrane proteins function as inhibitors of their cognate transcription regulator proteins, we will examine variety of potential posttranslational inhibitory control mechanisms and map the key residues in LRS proteins responsible for mediating the inhibition. Protein-protein interaction studies will determine whether LRS membrane proteins exert their function directly. 2) To determine how concurrent activation of the HdrRM and BrsRM LRS triggers a cell death pathway, we will test key aspects of a positive feedback cross-regulation model between LRS. Promoter binding studies will be correlated with transcriptional output responses.