PII: multiple homologs of a global regulator

PII：全球监管机构的多个同源物

• 批准号: 6946422
• 负责人: GARY Paul ROBERTS
• 金额: $ 18.69万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6946422
• 关键词: Rhodospirillum; bacterial proteins; gene mutation; microorganism metabolism; nitrogen metabolism; protein isoforms; protein protein interaction; protein sequence; protein structure function; receptor; transcription factor

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

描述（由申请人提供）：PII（GLNB）蛋白家族的成员是最广泛的调节蛋白之一，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不仅对其分布都很重要，而且对于已显示在氮调节的各个方面以及碳和氮利用的平衡方面发挥了关键作用。在过去的几年中，该提案试图利用这一提议的三个非常重要的发展：该家族两个成员的晶体结构已经解决，已经证明许多生物具有多个同源物，并且不同生物体中的同源物已与不同的生物化学功能有关。这些提案的关键问题和重点是这些不同的生化作用的分子基础。该提案将通过我们最近的观察结果来解决这个问题，即rhodospirillum rubrum具有三个同源物（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易于测定的Vivo函数。这提供了一个出色的模型系统，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PII（GLNB）同源物在这些角色中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同源物的临界区域将具有生物学意义，尤其是当对它们相互作用的蛋白质的更好理解时。在获得这些信息之前，我们无法理解PII家族的代谢角色。例如，只有这样的信息才能解释PII同源物中常见的翻译后尿素的作用。鉴于PII序列在许多生物学中的极端保存，这是一个合理的假设，即rubrum的PII同源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