UNDERSTANDING THE DESIGN OF MOLECULAR MOTORS
UNDERSTANDING THE DESIGN OF MOLECULAR MOTORS
批准号:
2909277
负责人:
JOHN M. MURRAY
金额:
$10.59万
依托单位国家:
美国
项目类别:
财政年份:
1999
资助国家:
美国
项目状态:
已结题
起止时间:
1999-09-30 至 2001-08-31
中文摘要
描述(改编自摘要):定向移动是定义之一
生活的特点。当我们怀疑某物是否活着时,我们通常会检查
看看它是不是在移动。在一个细胞内,我们发现了一个惊人的集合
产生运动的最奇妙的系统。这些生物马达是
值得研究的不仅仅是他们作为杰作的内在趣味
“纳米技术”,但因为它们的功能对正常健康至关重要。
基于微管的运动的重要例子包括染色体的运动
在细胞分裂过程中,各种细胞内膜的移位绑定
细胞器,以及将物质从神经元细胞体运输到
它们遥远的终点站。
关于这些电机系统的基本信息具有不同寻常的直接和
与人类健康直接相关。干扰的代理
基于微管的运动系统在人类中有治疗应用:
秋水仙碱,用于痛风性关节炎;长春新碱,长春花碱和紫杉醇,
用于抗多种肿瘤的有丝分裂作用;
灰黄霉素,一种抗真菌药物;以及其他。除了这些药用用途外,
影响基于微管的运动装置的药物对
人类健康在同样重要的非治疗方面,例如他们的
广泛用作杀虫剂和杀菌剂。
这项研究的目标是发现,在三维原子结构方面,如何
作为基于微管的分子马达的蛋白质会产生运动,这是为什么
不同的马达以非常不同的方式运动。研究主要集中在两个方面
以微管为基础的马达,动蛋白和NCD,向相反的方向移动。
目标是从这两个马达开始,创建一个新马达的库
具有不同的运动特性,然后确定它们的结构,从而
为了阐明区别于生物的结构特征
运动行为的重要特征类。
英文摘要
DESCRIPTION (Adapted from abstract): Directed movement is one of the defining
characteristics of life. When we wonder if something is alive, we usually check
to see if it is moving. Within a single cell we find an astounding collection
of the most marvelous systems for producing motion. These biological motors are
worthy of study not only for their intrinsic interest as masterpieces of
"nanotechnology", but because their function is crucial for normal health.
Important examples of microtubule-based motion include movement of chromosomes
during cell division, the translocation of various intracellular membrane bound
organelles, and the transport of materials from the cell body of neurons to
their distant termini.
Basic information about these motor systems has an unusually direct and
immediate connection to human health. Agents that interfere with
microtubule-based motile systems have therapeutic applications in humans:
colchicine, used for in gouty arthritis; vincristine, vinblastine, and taxol,
used for their anti-mitotic effects against a variety of neoplasms;
griseofulvin, an anti-fungal agent; and others. Besides these medicinal uses,
agents that affect the microtubule-based motile apparatus are significant for
human health in equally important non-therapeutic ways, such as their
widespread use as pesticides and fungicides.
The goal of this research is to discover, in terms of 3D atomic structure, how
proteins that act as microtubule-based molecular motors produce motion, and why
different motors move in very different ways. The research focuses on two
microtubule-based motors, kinesin and ncd, which move in opposite directions.
The aim is to create, starting from these two motors, a library of new motors
with different motile properties, then determine their structure, and thereby
to elucidate the structural features that distinguish the biologically
important characteristic classes of motile behavior.
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