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

直到最近，大多数细菌都被认为是单细胞生物，其中几乎没有细胞组织。它们不包含细胞器，如线粒体或细胞核，因此不认为细菌细胞内的蛋白质是专门组织的。然而，在过去的十年里，这种情况发生了根本性的变化，这主要是由于对细胞分裂的研究，现在很明显，蛋白质在细胞内有非常特定的位置，这些位置可以急剧而迅速地变化。最近的第二个主要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（如果不是大多数的话）蛋白质是多蛋白质复合物的一部分。这些复合物的成分倾向于反映功能相关蛋白的活性，它们也可能定位于细胞内的特定位置。此外，这些位置还可以根据环境和细胞的代谢状态而变化。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的膜蛋白AmtB，它作为一种通道，允许铵进入细胞。这个Amt蛋白家族在从细菌到人类的生物体中无处不在。此外，我们已经证明氨通过该通道的通量是由调节蛋白GlnK的动态定位控制的。在铵充足的时候，GlnK以这种方式与AmtB结合，从而物理地阻止氨进入细胞，当细胞对铵的需求再次上升时，这种情况就会逆转。在这项研究中，我们计划调查多蛋白复合物是否是细菌实现和调节铵和其他氮源代谢的共同特征。这样的工作对我们理解细菌——地球上最常见的生命形式——控制自身生长的方式至关重要。它还可以在未来发现新的方法，我们可以控制这种生长，例如在致病菌中。

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.