Piggy-backing the bacterial chromosome: positioning of protein complexes by chromosome segregation

搭载细菌染色体：通过染色体分离定位蛋白质复合物

• 批准号: BB/L002507/1
• 负责人: Judith Armitage
• 金额: $ 44.1万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL002507%2F1
• 关键词: Piggy; backing; bacterial; chromosome; positioning

When a cell divides, in general it produces a reasonable replica of itself. As the cell grows it makes new proteins, so that, before division it is reasonable to assume it has twice as many proteins as the initial cell. When that cell divides each daughter needs a chromosome to make those proteins, but are the proteins just a free soup that gets randomly divided between the daughter cells? That may be the case for some proteins, but other proteins need to be divided with partner proteins in the right ratio to work. This can be done by making tight, stable complexes that get divided together, but other groups of proteins need mechanisms that ensure each daughter cell has the correct proteins in the correct ratio. Membranes have long been know to be provide a framework for allowing proteins to come together, organising receptor proteins that respond to changes in the external world into interacting protein complexes. What about proteins that are soluble and do not respond to the external environment-how to they organise and how do cells ensure daughter cells inherit the right number of complexes. It has recently been realised that in bacterial cells some protein complexes can "piggy-back" on the duplicated and segregating chromosomes, with a protein loosely covering the chromosome surface and also interacting with a complex of proteins. As the chromosome segregates this protein carries this large protein "cargo" to the daughter cell. The protein which loosely associates with the chromosome is related to proteins known to also ensure daughter cells inherit the right genetic material and it is now clear that bacteria use this system to segregate a wide range of protein complexes needed in the correct ratio to function properly. As this is a common system across bacteria, it could be harnessed to organise other protein complexes between bacteria. In many metabolic pathways efficient rates are achieved when proteins are closely associate ensuring local high concentrations and fast substrate transfer. If these pathways are expressed in alien systems the proteins are often diffuse and disorganised, resulting in inefficient rates of activity. In addition many proteins function with partner proteins and to understand how they work ideally their structures need to be characterised when bound, but usually the proteins are purified individually and mixed or when expressed individually they are insoluble. It is possible we can use this natural system for segregating protein complexes to keep other proteins in functional complexes and at high local concentrations. Using this reduced system we could either use the system in synthetic biology for allowing a daughter cells to segregate proteins in functional but high ratios for a pathway to efficiently produce a desired product or it will allow expression of protein partners in an environment that will allow their isolation and structural analysis. To be able to harness this newly identified mechanism we need to understand the essential components holding the proteins together as complexes, causing the protein complexes to duplicate and the association with the chromosome on the chromosome associated protein.

当一个细胞分裂时，通常它会产生一个合理的自身复制品。随着细胞的生长，它会产生新的蛋白质，因此，在分裂之前，可以合理地假设它的蛋白质数量是原始细胞的两倍。当细胞分裂时，每个子细胞都需要一条染色体来制造这些蛋白质，但蛋白质只是一个免费的汤，随机分配给子细胞吗？这可能是某些蛋白质的情况，但其他蛋白质需要与伴侣蛋白质以正确的比例分开才能发挥作用。这可以通过制造紧密、稳定的复合物并将其分开在一起来实现，但其他蛋白质组需要确保每个子细胞以正确比例具有正确蛋白质的机制。长期以来，人们一直认为膜提供了一个框架，允许蛋白质聚集在一起，将对外部世界变化做出反应的受体蛋白组织成相互作用的蛋白质复合物。那些可溶性的、对外界环境不起反应的蛋白质又是怎样的呢？它们是如何组织的？细胞又是如何确保子细胞继承正确数量的复合物的？最近人们意识到，在细菌细胞中，一些蛋白质复合物可以“搭载”在复制和分离的染色体上，蛋白质松散地覆盖在染色体表面，并与蛋白质复合物相互作用。当染色体分离时，这种蛋白质携带这种大蛋白质“货物”到子细胞。与染色体松散结合的蛋白质与已知的蛋白质有关，这些蛋白质也确保子细胞继承正确的遗传物质，现在很清楚，细菌使用这个系统来分离各种蛋白质复合物，这些蛋白质复合物需要正确的比例才能正常发挥作用。由于这是细菌之间的一个共同系统，因此可以利用它来组织细菌之间的其他蛋白质复合物。在许多代谢途径中，当蛋白质紧密结合时，可实现有效速率，确保局部高浓度和快速底物转移。如果这些途径在外来系统中表达，蛋白质通常是分散和无序的，导致活性效率低下。此外，许多蛋白质与伴侣蛋白一起发挥作用，为了了解它们如何理想地发挥作用，需要在结合时表征它们的结构，但通常蛋白质被单独纯化并混合，或者当单独表达时，它们是不溶的。我们有可能使用这种天然系统分离蛋白质复合物，以使其他蛋白质保持在功能复合物中并处于高局部浓度。使用这种简化的系统，我们可以在合成生物学中使用该系统，以允许子细胞以功能性但高比率分离蛋白质，以用于有效产生所需产物的途径，或者它将允许蛋白质伴侣在允许其分离和结构分析的环境中表达。为了能够利用这种新发现的机制，我们需要了解将蛋白质结合在一起作为复合物的基本成分，导致蛋白质复合物复制以及与染色体相关蛋白质上的染色体的关联。

项目成果

Cellular targeting and segregation of bacterial chemosensory systems.

• DOI: 10.1093/femsre/fuy015
• 发表时间: 2018-06
• 期刊: FEMS microbiology reviews
• 影响因子: 11.3
• 作者: Emilia M. F. Mauriello;Christopher W. Jones;A. Moine;J. Armitage

Ribo-attenuators: novel elements for reliable and modular riboswitch engineering.

• DOI: 10.1038/s41598-017-04093-x
• 发表时间: 2017-07-04
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Folliard T;Mertins B;Steel H;Prescott TP;Newport T;Jones CW;Wadhams G;Bayer T;Armitage JP;Papachristodoulou A;Rothschild LJ
• 通讯作者: Rothschild LJ

Structure of bacterial cytoplasmic chemoreceptor arrays and implications for chemotactic signaling.

细菌细胞质化学感受器阵列的结构及其对趋化信号传导的影响。

• DOI: 10.7554/elife.02151
• 发表时间: 2014-03-25
• 期刊: eLife
• 影响因子: 7.7
• 作者: Briegel A;Ladinsky MS;Oikonomou C;Jones CW;Harris MJ;Fowler DJ;Chang YW;Thompson LK;Armitage JP;Jensen GJ
• 通讯作者: Jensen GJ