PII: multiple homologs of a global regulator

描述(申请人提供)：PII(GlnB)蛋白家族的成员是分布最广泛的调节蛋白之一，主要参与细菌、古菌和一些植物的中央氮调节。这一蛋白质家族不仅对其分布具有重要的生物学意义，而且在氮调节和碳氮利用平衡的各个方面都发挥着关键作用。在过去的几年里，这一提议试图利用的三个非常重要的发展：解决了这个家族两个成员的晶体结构，许多生物被证明有不止一个同系物，以及不同生物中的同源物涉及到相当不同的生化功能。一个关键问题，也是这项提议的一个焦点，是这些不同生化作用的分子基础。这一建议将利用我们最近的观察来解决这个问题，即红色红螺菌有三个同源物(命名为GlnB、GlnJ和GlnK)，具有相当相似的序列，但至少有四个不同的在体内易于检测的功能。这为识别这些同源物中具有重要功能的残基提供了一个很好的模型系统，将它们与特定的生物学角色相关联，并最终确定在这些角色中与PII(GlnB)同源物相互作用的特定受体蛋白。 识别参与不同蛋白质相互作用的PII同系物的关键区域将具有生物学意义，特别是当结合更好地了解它们与之相互作用的蛋白质时。在我们准确掌握这些信息之前，我们无法理解PII家族的不同代谢作用。例如，只有这样的信息才能解释PII同系物中常见的翻译后尿苷基化的作用。鉴于PII序列在生物学上的极端保守性，一个合理的假设是，参与红色红曲霉PII同系物相互作用的临界表面也将作为其他PII同源物的重要区域

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