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

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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.