Co-translational assembly of multiprotein complexes: a systems biology approach

构建一个细胞的信息是在它的DNA中携带的。为了使用，DNA的一部分需要复制到另一种称为RNA的分子中，然后它可以“翻译”成蛋白质。蛋白质是直接构建细胞并使其发挥功能的成分。蛋白质本身不起作用。它们相互附着形成复杂的机器，有时由数十种蛋白质组成。相互结合并一起工作的蛋白质组被称为蛋白质复合物。关于蛋白质复合物是如何由细胞构建的，我们知之甚少。一种可能性是蛋白质首先被制造出来，然后相互附着形成复合物。第二种可能性是蛋白质在细胞中合成时开始相互结合。有一些已知的蛋白质复合物是以第二种方式制备的。然而，由于检测这种现象非常困难，因此尚不清楚细胞是否通常选择这种制造蛋白质复合物的方式。我最近开发了一些方法，可以很容易地判断复合体的形成是否以这种方式进行。该项目的目的是将这种方法应用于许多具有非常不同功能的蛋白质复合物，以了解细胞如何构建蛋白质复合物。为什么这对细胞很重要？有几个原因。蛋白质需要相互识别以形成蛋白质复合物，它们可以相互识别，因为它们具有相互适合的特定形状（类似于钥匙适合锁）。蛋白质的形状在制造过程中会发生变化，有些蛋白质在完全制造后可能不再相互适合。此外，一些蛋白质在游离时可能对细胞有毒（但当它们是正确复合物的一部分时是有用的）。避免这种情况的一个好方法是尽快将蛋白质放入复合物中（甚至在它们完成之前）。我们将使用简单的酵母细胞来研究这些问题。酵母细胞与我们非常相似，我们从它们身上学到的东西对了解人体很有用。由于蛋白质复合物对细胞所做的几乎所有事情都很重要，我们希望了解它们是如何由细胞制造的，这将有助于了解它们的功能以及它们在疾病期间出现的问题。

The information to build a cell is carried in its DNA. To be used, a portion of DNA needs to be copied into another molecule called RNA, from which it can be 'translated' into a protein. Proteins are the components that directly build the cell and make it function. Proteins do not work on their own. They attach to each other to form complicated machines, sometimes made up of dozens of proteins. Groups of proteins that are bound to each other and work together are called protein complexes. Not much is known about how protein complexes are built by cells. One possibility is that proteins are first made, and then attach to each other to form a complex. A second possibility is that the proteins start to bind to each other while they are being made in the cell. There are a few known cases of protein complexes that are made in the second way. However, because detecting this phenomenon is very difficult, it is not known if cells usually choose this way of making protein complexes. I have recently developed methods that make it easy to tell if the formation of a complex proceeds in this way. The aim of this project is to apply this method to many protein complexes with very different functions, in order to understand how cells build protein complexes. Why is this important for a cell? There are several reasons. Proteins need to recognise each other to form protein complexes, and they can recognise each other because they have specific shapes that fit into each other (similar to a key fitting into a lock). The shape of a protein changes as it is being made, and it is possible that some proteins can no longer fit into each other once they are completely made. Also, some proteins may be toxic for the cell when they are free (but useful when they are part of the correct complex). A good way to avoid this is to put the proteins in the complex as soon as possible (even before they are finished). We will study these questions using simple yeast cells. Yeast cells are similar enough to us that what we can learn from them is useful to understand the human body. Because protein complexes are important for almost everything a cell does, we hope that understanding how they are made by cells will help understand how they function and what goes wrong with them during disease.