PII: multiple homologs of a global regulator

描述（由申请人提供）：PII （GlnB）蛋白家族成员是分布最广泛的调控蛋白之一，主要参与细菌、古细菌和一些植物的中心氮调控。该蛋白家族在生物学上的重要性不仅在于其分布，还在于其在氮调节和碳氮利用平衡的各个方面发挥的关键作用。在过去的几年中，本提案试图利用三个非常重要的进展：这个家族的两个成员的晶体结构已经解决，许多生物体已经被证明有不止一个同源物，不同生物体中的同源物已经涉及相当不同的生化功能。一个关键的问题，也是本提案的重点，是这些不同生化作用的分子基础。本文将利用我们最近的观察来解决这个问题，红红螺旋菌有三个同源物（命名为GlnB， GlnJ和GlnK），它们具有相当相似的序列，但在体内具有至少四种不同的易于测定的功能。这为识别这些同源物中功能重要的残基，将它们与特定的生物学作用联系起来，并最终确定在这些作用中与PII （GlnB）同源物相互作用的特定受体蛋白提供了一个很好的模型系统。

DESCRIPTION (provided by applicant): The members of the PII (GlnB) protein family are among the most broadly distributed regulatory proteins and are primarily involved in central nitrogen regulation in bacteria, archaea and in some plants. This protein family is biologically important not only for its distribution, but also for the critical roles that it has been shown to play in all aspects of nitrogen regulation and the balancing of carbon and nitrogen utilization. In the past few years, three very significant developments have occurred that this proposal seeks to take advantage of: The crystal structures of two members of this family have been solved, many organisms have been shown to have more than one homolog, and homologs in different organisms have been implicated in rather different biochemical functions. A critical issue, and a focus of this proposal, is the molecular basis of these different biochemical roles. This proposal will address this issue using our recent observation that Rhodospirillum rubrum has three homologs (named GlnB, GlnJ, and GlnK), with rather similar sequences, but with at least four different readily assayed functions in vivo. This provides an excellent model system for identifying functionally important residues in these homologs, correlating them with specific biological roles and eventually determining the specific receptor proteins that interact with the PII (GlnB) homologs in these roles. Identification of the critical regions of the PII homologs involved in different protein interactions will be of biological importance, especially when coupled with a better understanding of the proteins with which they interact. We cannot understand the diverse metabolic roles of the PII family until we have precisely this information. Only such information will, for example, explain the role of the post-translational uridylylation that is common among PII homologs. Given the extreme conservation of PII sequence across much of biology, it is a reasonable hypothesis that critical surfaces involved in the interactions of the PII homologs of R. rubrum will serve as important regions in other PII homologs as well