Transporter, Creator, Destroyer: How is the kinesin motor domain tuned to specific functions?

在细胞内发现了一种叫做细胞骨架的蛋白质纤维网络。细胞骨架就像人体的骨骼一样，为细胞提供了一个支架，使它们能够保持其功能所需的形状。此外，像我们的骨骼一样，细胞骨架提供了一个在细胞内产生作用力的平台。这与我们的肌肉通过拉动我们的骨骼来产生力量的方式类似。与我们的骨骼不同，细胞骨架是高度动态的。组成细胞骨架的细丝可以在几秒钟内形成、分解和重塑。细胞骨架由三种不同类型的细丝组成，其中一种是微管细胞骨架。顾名思义，微管是直径小于万分之一毫米的长管。微管是由一种叫做“微管蛋白”的积木构成的。蛋白质微管蛋白具有令人着迷的能力，可以多次自发地组装、分解和重新组装。通过在微管蛋白构建块上添加荧光染料标签，并使用强大的显微镜，我们可以看到由微管蛋白形成的微管，并观察它们的组装和拆卸。通过这种方式，我们可以观察到目前在我们自己的细胞中正在发生的一个过程，但我们可以孤立地观察它，这样我们就可以在没有细胞其他部分的情况下观察它。这为我们提供了一个极好的机会来研究和了解微管组装和分解的动力学。微管本身及其组装和分解的能力在我们的细胞中都发挥着至关重要的功能。微管起着轨道的作用，被称为运动蛋白的蛋白质在上面行走，允许它们将货物从制造货物的地方运送到细胞需要的地方。微管的组装和拆解能力使它们能够形成细胞暂时所需的结构，例如细胞分裂时分离复制DNA所需的装置。为了创造这种被称为有丝分裂纺锤体的装置，必须仔细控制微管的组装和拆卸。因此，细胞中含有一系列蛋白质，负责协调微管的构建和破坏。令人惊讶的是，一种分解微管的蛋白质是运动蛋白，它的结构与沿着微管轨道行走的运动蛋白相同。结构上的同源蛋白质如何执行如此不同的工作是一个令人着迷的问题。使它们执行不同功能的运动蛋白的成分还没有完全被了解。为了回答这个问题，我们将移除运动域中的运动蛋白的部分，并在不同运动蛋白的运动域之间交换部分，并观察对它们行为的影响。这将使我们能够识别重要的部分，它们是如何工作的，以及我们如何控制它们。微管和运动蛋白是维持我们的细胞，从而保持我们的身体有序并能够正常生长和功能的机制的重要组成部分。也许它们最重要的作用是控制细胞分裂。控制细胞分裂的机制失败会导致多种人类疾病，包括癌症和发育障碍。我们对参与细胞分裂控制的蛋白质了解得越多，我们就越有能力防止和修复这一过程的中断。

A network of proteinacous filaments, called the cytoskeleton, is found within cells. The cytoskeleton, like the bone skeleton of the human body, provides cells with a scaffold allowing them to maintain the shape required for their function. Also, like our bone skeleton, the cytoskeleton provides a platform against which to generate forces within the cell. This works in a similar way to the way in which our muscles generate forces by pulling against our bones. Unlike our bone skeleton, the cytoskeleton is highly dynamic. The filaments that make up the cytoskeleton can be formed, broken down and reformed within seconds. The cytoskeleton comprises three different types of filament, one of which is the microtubule cytoskeleton. Microtubules, as the name suggests, are long tubes with a diameter of less than one ten-thousandth of a millimetre. Microtubules are constructed from a building block called 'tubulin'. The protein tubulin possesses the fascinating ability to spontaneously assemble, disassemble, and reassemble many times over. By adding a fluorescent dye label to the tubulin building blocks and using powerful microscopes, we can see the microtubules formed from tubulin and watch their assembly and disassembly. In this way, we can observe a process that is happening right now in our own cells, but in isolation so that we can observe it without any other parts of the cell around. This provides us with a wonderful opportunity to study and understand the dynamics of microtubule assembly and disassembly.Both the microtubules themselves and their ability to assemble and disassemble perform vital functions in our cells. Microtubules act as rails upon which proteins, called kinesins (from the word kinetic, indicating their ability to move) walk, allowing them to carry cargo from where it is made to where it is needed in the cell. The ability of microtubules to assemble and disassemble allows them to form structures required temporarily by cells, such as the apparatus required to separate the duplicate DNA when a cell divides. To create this apparatus, known as the mitotic spindle, the assembly and disassembly of microtubules must be carefully controlled. Therefore, the cell contains an array of proteins responsible for coordinating the building and destruction of microtubules. Amazingly, one protein that disassembles microtubules is a kinesin and has the same structure as kinesins that walk along microtubule rails. How structurally homologous proteins can carry out such different jobs is a fascinating question. The components of kinesins that allow them to carry out different functions are not fully understood. To answer this question, we will remove parts of the kinesin motor domain and also swap parts between the motor domains of different kinesins and watch the effect on their behaviour. This will allow us to identify the important pieces, how they work and how we can control them.Microtubules and kinesins are a vital part of the mechanisms that keep our cells, and therefore our bodies, in order and able to grow and function correctly. Perhaps their most important role is in controlling cell division. Failure of the mechanisms controlling cell division results in multiple human diseases, including cancer and developmental disorders. The more we can find out about the proteins involved in the control of cell division the more power we have to prevent and repair disruption of this process.