生物谷报道：动力蛋白是细胞质中的一个大的蛋白质复合体，在有丝分裂中具有复杂的功能，参与核膜破裂、纺锤体组装、染色体运动、纺锤体检查点失活等。它也在细胞内膜细胞器（如线粒体，高尔基体）的运输中有重要功能，线粒体主要为细胞产生能量，而高尔基体则合成蛋白质。目前对作用机理所知甚少。
北卡罗来纳大学医学院11月27日发布消息，称该校已提出了新的结构模型，揭开了动力蛋白作用机制的迷团。研究部分由肌萎缩学会和美国心脏学会资助，结果发表于11月22日的网上《国家科学院工作进展年初版》(the Proceedings of the National Academy of Sciences Early Edition)。
研究主持者生化和生物物理学的助理教授Nikolay V. Dokholyan博士说：“动力蛋白将三磷酸腺苷（ATP，细胞的主要能源）转化为机械力，但因为科学家缺乏对动力蛋白结构的全面而详细的了解，所以对转化的机制基本上不了解。这种转化类似于发动机驱动汽车，我们知道发动机在前面通过燃烧汽油而提供能量，但我们不知道它是怎样让车轮动起来的。”
该校生物信息学及计算生物学工程的主任，药理学副教授Timothy Elston进一步解释：“动力蛋白中与ATP结合获取能量的部位距离产生动力的部位非常远，动力一定经过了长距离的传输，而这正是令人不解之处。”
Dokholyan的实验室里的研究生Adrian W.R. Serohijos是论文的第一作者，他通过大量的原子水平分辨率的模拟技术，确认了动力蛋白里有一个弹簧样的“缠绕线圈”，连接动力部位和ATP结合部位，这是“以往研究都完全没有发现的。”Dokholyan说，“动力蛋白转化机械能，运输象线粒体这样大的细胞器，从而完成各种功能，如产生能量，生产蛋白质及维护细胞正常。以及在细胞分裂中，提供了机械能协助染色体的分离。”
虽然研究结果不能马上用于临床，但作者提到动力蛋白突变与一些神经退变及肾脏病有关。它与一种特殊的调节蛋白的相互作用，可损害神经细胞传导，从而产生类似于肌萎缩侧索硬化的症状。
英文原文：
UNC Scientists Solve Mystery of How Largest Cellular Motor Protein Powers Movement
11/27/06 -- Scientists now understand how an important protein converts chemical energy to mechanical force, thus powering the process of cell division, thanks to a new structural model by University of North Carolina at Chapel Hill researchers.
The structural model helps solve a scientific mystery: how the protein dynein fuels itself to perform cellular functions vital to life. These functions include mitosis, or cell division into identical cells.
Dynein uses energy derived from ATP, or adenosine triphosphate, a molecule that is the principal form of energy for cells. The lack of a comprehensive and detailed molecular structure for dynein has kept scientists largely in the dark about how the protein converts ATP into mechanical force, said Dr. Nikolay V. Dokholyan, assistant professor of biochemistry and biophysics in the UNC School of Medicine.
Dokholyan said the dynein puzzle is similar to figuring out how auto engines make cars move.
"You have an engine up front that burns gas, but we didn't know how the wheels are made to move."
Dr. Timothy Elston, associate professor of pharmacology and director of the School of Medicine?s bioinformatics and computational biology program, explains further."One of the unknowns about dynein was that the molecular site where chemical energy is initially released from ATP is very far away from where the mechanical force occurs. The mechanical force must be transmitted over a large distance."
The study was published online Nov. 22 in the Proceedings of the National Academy of Sciences Early Edition. The work was supported in part by grants from the Muscular Dystrophy Association and the American Heart Association.
Using a variety of modeling techniques that allowed resolution at the level of atoms, Adrian W.R. Serohijos, a graduate student in Dokholyan?s lab and first author of the study, identified a flexible, spring-like "coiled-coil" region within dynein. It couples the motor protein to the distant ATP site.
"This dynein coiled-coil was completely missing from all previous studies. We saw it could allow a very rapid transduction of chemical energy into mechanical energy," Dokholyan said.
Conversion to mechanical energy allows dynein to transport cellular structures such as mitochondria that perform specific jobs such as energy generation, protein production and cell maintenance. Dynein also helps force apart chromosomes during cell division.
"Dividing cells must separate their chromosomes and something has to generate the force to move chromosomes apart. Dynein provides the mechanical energy to do that," Doholyan said.
While the research offers no immediate application to human disease, the authors noted that mutations of dynein have been implicated in some neurodegenerative and kidney disorders. Dokholyan pointed out that disruption of dynein's interaction with a particular regulator protein causes defects in nerve cell transmission and mimics the symptoms of people with amyotrophic lateral sclerosis (ALS).
Source: University of North Carolina School of Medicine
