Structure and function of the SUMO specific protease SENP7

我们之所以是我们，是因为我们所表达的基因。当翻译成蛋白质时，这些基因产物具有催化化学反应，建立细胞结构和促进细胞内物质运动的作用。简单的线虫大约有13000个基因，但尽管我们人类是复杂得多的生物，我们的基因数量只有线虫的两倍。显然，基因的数量不能解释我们急剧增加的复杂性。然而，增加复杂性的一种方法是将蛋白质连接在一起产生新的蛋白质。泛素类蛋白家族可以与多种蛋白质共价连接，从而极大地增加了我们基因产物的复杂性。这必须在非常明确的条件下完成，在这种条件下，选择特定的底物，由特定的乌布黄素样蛋白进行修饰。这些途径的重要性体现在当这些过程失败或执行不准确时导致的疾病状态的数量上。任何特定蛋白质的修饰状态都源于偶联和解偶联之间的微妙平衡。在小泛素样修饰剂SUMO的情况下，解偶联是由SUMO特异性蛋白酶介导的。本文提出的工作目的是了解SUMO特异性蛋白酶SENP7如何选择SUMO修饰的靶标进行解偶联。这种特殊的酶具有独特的特性，可以说明泛素样蛋白质如何解共轭的重要原理。这项工作将在邓迪大学新詹姆斯·布莱克中心的生命科学学院进行，并将与圣安德鲁斯大学的科学家合作

We are what we are because of the genes we express. When translated into proteins these gene products have roles in catalysing chemical reactions, establishing the architecture of the cell and facilitating movement of materials within the cell. Simple nematode worms have about 13,000 genes, but although we humans are vastly more complex organisms we only have about twice the number of genes that the nematodes have. Clearly then the number of genes cannot explain our vastly increased complexity. However one way in which complexity can be increased is to link proteins together to generate new proteins. The ubiquitin like family of proteins can be covalently linked to a wide variety of proteins thus hugely increasing the complexity of our gene products. This has to be done under very well defined conditions where specific substrates are selected for modification by particular uibuqitin-like proteins. The importance of these pathways is manifest in the number of disease states that result when these processes fail or are carried out inaccurately. Modification status of any particular protein results from a delicate balance between conjugation and deconjugation. In the case of the Small Ubiquitin-like Modifier, SUMO, deconjugation is mediated by SUMO specific proteases The objective of the work proposed here is to understand how SUMO modified targets are selected for deconjugation by the SUMO specific protease SENP7. This particular enzyme has unique properties that could illustrate important principles in how ubiquitin-like proteins are deconjugated. The work will be carried out at the College of Life Sciences in the new James Black Centre at the University of Dundee and would involve collaborations with scientists at St Andrews University