The role of protein complexes and protein localisation in regulation of bacterial nitrogen metabolism

蛋白质复合物和蛋白质定位在调节细菌氮代谢中的作用

• 批准号: BB/E022308/1
• 负责人: Mike Merrick
• 金额: $ 44.72万
• 依托单位: John Innes Centre
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE022308%2F1
• 关键词: role; protein; complexes; localisation; regulation

Until relatively recently most bacteria were considered to be single celled organisms within which there was little, if any, cellular organisation. They do not contain organelles such as mitochondria or nuclei and consequently it was not considered that proteins within the bacterial cell were specifically organised. However in the last ten years this picture has changed radically, largely as a consequence of studies on cell division where it is now apparent that proteins have very specific locations within the cell and that these can change dramatically and rapidly. A second major recent advance has been the ability to identify protein-protein interactions in bacteria on a whole cell scale and thereby to recognise that many, if not most, proteins are part of multi-protein complexes. The components of these complexes tend to reflect the activities of functionally related proteins and they may also be localised to specific positions within the cell. Furthermore these positions can also change according to the environment and metabolic state of the cell. Ammonium is a fundamental nitrogen source for most bacteria and in our recent studies we have described in some detail a novel membrane protein AmtB that acts as a channel to allow ammonium to enter the cell. This family of Amt proteins is ubiquitous in living organisms being found from bacteria to man. Furthermore we have shown that the flux of ammonia through this channel is controlled by the dynamic localisation of a regulatory protein, GlnK. In times of ammonium sufficiency GlnK binds to AmtB in such a way as to physically block the movement of ammonia into the cell, and this is reversed when the cellular demand for ammonium rises again. In this research we plan to investigate whether multi-protein complexes are a common feature of the way in which bacteria achieve and regulate the metabolism of ammonium and other nitrogen sources. Such work is fundamental to our understanding of the way in which bacteria, the most common life form on the earth, control their growth. It could also in the future identify new ways in which we might control that growth e.g. in pathogenic bacteria.

直到最近，大多数细菌还被认为是单细胞生物体，其中几乎没有细胞组织。它们不包含线粒体或细胞核等细胞器，因此不认为细菌细胞内的蛋白质是特定组织的。然而，在过去的十年里，这种情况发生了根本性的变化，这在很大程度上是因为对细胞分裂的研究，现在很明显，蛋白质在细胞内具有非常特定的位置，而且这些位置可能会发生巨大而迅速的变化。最近的第二个重大进展是能够在整个细胞尺度上识别细菌中的蛋白质-蛋白质相互作用，从而认识到许多蛋白质(如果不是大多数的话)是多蛋白质复合体的一部分。这些复合体的成分往往反映了与功能相关的蛋白质的活性，它们也可能定位于细胞内的特定位置。此外，这些位置也可以根据环境和细胞的新陈代谢状态而变化。铵是大多数细菌的基本氮源，在我们最近的研究中，我们详细描述了一种新型的膜蛋白AmtB，它充当了允许铵进入细胞的通道。这个AMT蛋白家族普遍存在于从细菌到人类的生物体中。此外，我们还表明，通过这一通道的氨通量受调节蛋白GlnK的动态定位控制。在氨充足的时候，GlnK以一种物理上阻止氨进入细胞的方式与AmtB结合，当细胞对铵的需求再次增加时，情况就会逆转。在这项研究中，我们计划调查多蛋白复合体是否是细菌获得和调节铵和其他氮源代谢的共同特征。这些工作对于我们理解细菌--地球上最常见的生命形式--如何控制它们的生长是至关重要的。它还可以在未来确定我们可能控制这种增长的新方法，例如在病原体中。

项目成果

Association and dissociation of the GlnK-AmtB complex in response to cellular nitrogen status can occur in the absence of GlnK post-translational modification.

• DOI: 10.3389/fmicb.2014.00731
• 发表时间: 2014
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Radchenko MV;Thornton J;Merrick M
• 通讯作者: Merrick M

Post-translational modification of P II signal transduction proteins.

• DOI: 10.3389/fmicb.2014.00763
• 发表时间: 2014
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Merrick M