Elucidating the mechanism of microtubule depolymerisation by Kip3D kinesin

阐明 Kip3D 驱动蛋白微管解聚机制

• 批准号: BB/D008921/1
• 负责人: Carolyn Moores
• 金额: $ 38.16万
• 依托单位: Birkbeck, University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD008921%2F1
• 关键词: Elucidating; mechanism; microtubule; depolymerisation; Kip3D

Your body has a skeleton that gives you strength and support and allows you to move. The cells of your body also need strength and support, so cells also have a skeleton called the cytoskeleton. The cytoskeleton is built from 3 different types of fibre-like structures: one of these is called the microtubule. The aim of this project is to understand some of the functions that microtubules perform in cells, especially in cells that are multiplying in number. This is a process called mitosis. It is important to understand as much about mitosis as we can because it is very important for human health in lots of different ways. We all start life as just one cell and it is only after cells multiply billions of times that there are enough cells to make a complete human body. When mitosis goes wrong, the human body may not develop properly and this can cause birth defects and severe health problems. Also, when cells multiply out of control, cancer can occur. The more we understand about how cells multiply and what enzymes are important for controlling this multiplication, the better we will be able to find ways to stop mitosis from going wrong. The microtubule cytoskeleton is different from the human skeleton because it can change shape depending on what the cell needs to do or be. For example, a cell that is going through mitosis has a very different shape and behaviour from a cell that is not. Cells use different types of enzymes to control the shape of the microtubule cytoskeleton. In this project, we want to understand how an enzyme called Kip3D controls microtubule shape. Kip3D is an microscopic motor that uses the energy from ATP to do work when it binds to microtubules. Kip3D uses the energy of ATP to pull microtubules to pieces (depolymerisation). This is especially important in mitosis when the organisation of the microtubule cytoskeleton is constantly changing to ensure that mitosis is successful. We will use an electron microscope - a very powerful kind of microscope that takes pictures at very high magnification - to see what Kip3D looks like when it interacts with microtubules. Looking at the structure of Kip3D bound to microtubules will help us understand how the Kip3D molecules use ATP to depolymerise microtubules. When we understand how individual molecules of Kip3D work, we will understand better how Kip3D functions in a multiplying cell this and will help us find new ways to treat human diseases like cancer.

你的身体有一个骨架，给你力量和支持，让你移动。你身体的细胞也需要力量和支持，所以细胞也有一个骨架，称为细胞骨架。细胞骨架由3种不同类型的纤维状结构组成：其中一种称为微管。该项目的目的是了解微管在细胞中执行的一些功能，特别是在数量繁殖的细胞中。这个过程叫做有丝分裂。尽可能多地了解有丝分裂是很重要的，因为它在很多方面对人类健康非常重要。我们都是从一个细胞开始生命的，只有在细胞繁殖数十亿倍之后，才有足够的细胞组成一个完整的人体。当有丝分裂出现问题时，人体可能无法正常发育，这可能导致出生缺陷和严重的健康问题。此外，当细胞繁殖失控时，癌症可能会发生。我们对细胞如何繁殖以及哪些酶对控制这种繁殖很重要了解得越多，我们就越能找到阻止有丝分裂出错的方法。微管细胞骨架与人类骨架不同，因为它可以根据细胞需要做什么或成为什么而改变形状。例如，正在进行有丝分裂的细胞与没有进行有丝分裂的细胞具有非常不同的形状和行为。细胞使用不同类型的酶来控制微管细胞骨架的形状。在这个项目中，我们想了解一种名为Kip 3D的酶如何控制微管形状。Kip 3D是一种微观马达，当它与微管结合时，利用ATP的能量做功。Kip 3D使用ATP的能量将微管拉成碎片（解聚）。这在有丝分裂中尤其重要，因为微管细胞骨架的组织不断变化以确保有丝分裂成功。我们将使用电子显微镜-一种非常强大的显微镜，可以在非常高的放大倍率下拍照-来观察Kip 3D与微管相互作用时的样子。观察与微管结合的Kip 3D的结构将有助于我们理解Kip 3D分子如何使用ATP解聚微管。当我们了解Kip 3D的单个分子如何工作时，我们将更好地了解Kip 3D如何在增殖细胞中发挥作用，并将帮助我们找到治疗癌症等人类疾病的新方法。