生物谷報(bào)道：動(dòng)力蛋白是細(xì)胞質(zhì)中的一個(gè)大的蛋白質(zhì)復(fù)合體,，在有絲分裂中具有復(fù)雜的功能，參與核膜破裂,、紡錘體組裝,、染色體運(yùn)動(dòng)、紡錘體檢查點(diǎn)失活等,。它也在細(xì)胞內(nèi)膜細(xì)胞器（如線粒體,，高爾基體）的運(yùn)輸中有重要功能，線粒體主要為細(xì)胞產(chǎn)生能量,，而高爾基體則合成蛋白質(zhì),。目前對作用機(jī)理所知甚少。
北卡羅來納大學(xué)醫(yī)學(xué)院11月27日發(fā)布消息,，稱該校已提出了新的結(jié)構(gòu)模型,，揭開了動(dòng)力蛋白作用機(jī)制的迷團(tuán)。研究部分由肌萎縮學(xué)會(huì)和美國心臟學(xué)會(huì)資助,，結(jié)果發(fā)表于11月22日的網(wǎng)上《國家科學(xué)院工作進(jìn)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學(xué)的助理教授Nikolay V. Dokholyan博士說：“動(dòng)力蛋白將三磷酸腺苷（ATP，細(xì)胞的主要能源）轉(zhuǎn)化為機(jī)械力,，但因?yàn)榭茖W(xué)家缺乏對動(dòng)力蛋白結(jié)構(gòu)的全面而詳細(xì)的了解,，所以對轉(zhuǎn)化的機(jī)制基本上不了解。這種轉(zhuǎn)化類似于發(fā)動(dòng)機(jī)驅(qū)動(dòng)汽車,，我們知道發(fā)動(dòng)機(jī)在前面通過燃燒汽油而提供能量,，但我們不知道它是怎樣讓車輪動(dòng)起來的。”
該校生物信息學(xué)及計(jì)算生物學(xué)工程的主任,，藥理學(xué)副教授Timothy Elston進(jìn)一步解釋：“動(dòng)力蛋白中與ATP結(jié)合獲取能量的部位距離產(chǎn)生動(dòng)力的部位非常遠(yuǎn),，動(dòng)力一定經(jīng)過了長距離的傳輸，而這正是令人不解之處,。”
Dokholyan的實(shí)驗(yàn)室里的研究生Adrian W.R. Serohijos是論文的第一作者,，他通過大量的原子水平分辨率的模擬技術(shù),，確認(rèn)了動(dòng)力蛋白里有一個(gè)彈簧樣的“纏繞線圈”，連接動(dòng)力部位和ATP結(jié)合部位,，這是“以往研究都完全沒有發(fā)現(xiàn)的,。”Dokholyan說，“動(dòng)力蛋白轉(zhuǎn)化機(jī)械能,，運(yùn)輸象線粒體這樣大的細(xì)胞器,，從而完成各種功能，如產(chǎn)生能量,，生產(chǎn)蛋白質(zhì)及維護(hù)細(xì)胞正常,。以及在細(xì)胞分裂中，提供了機(jī)械能協(xié)助染色體的分離,。”
雖然研究結(jié)果不能馬上用于臨床,，但作者提到動(dòng)力蛋白突變與一些神經(jīng)退變及腎臟病有關(guān)。它與一種特殊的調(diào)節(jié)蛋白的相互作用,，可損害神經(jīng)細(xì)胞傳導(dǎo),，從而產(chǎn)生類似于肌萎縮側(cè)索硬化的癥狀。
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
