PII: multiple homologs of a global regulator

描述（由申请人提供）：PII（GlnB）蛋白家族的成员是分布最广泛的调节蛋白，主要参与细菌、古细菌和某些植物中的中央氮调节。该蛋白质家族在生物学上具有重要意义，不仅因为它的分布，而且因为它在氮调节的各个方面以及碳和氮利用的平衡中所起的关键作用。在过去的几年里，有三个非常重要的发展，这个建议试图利用：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一个以上的同系物，在不同的生物体中的同系物已经被牵连在相当不同的生化功能。一个关键的问题，也是这个建议的焦点，是这些不同的生化作用的分子基础。该提案将利用我们最近的观察结果来解决这个问题，即红色红球藻有三个同源物（命名为GlnB，GlnJ和GlnK），具有相当相似的序列，但具有至少四种不同的易于在体内测定的功能。这提供了一个很好的模型系统，用于识别这些同源物中功能上重要的残基，将它们与特定的生物学作用相关联，并最终确定与这些作用中的PII（GlnB）同源物相互作用的特定受体蛋白。 鉴定参与不同蛋白质相互作用的PII同源物的关键区域将具有生物学重要性，特别是当与它们相互作用的蛋白质的更好理解相结合时。我们无法理解PII家族的不同代谢作用，直到我们有确切的信息。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酰化的作用。鉴于PII序列在生物学中的极端保守性，这是一个合理的假设，即参与R.红色也将作为其他PII同系物的重要区域

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