主题：【分享】对细胞蛋白工厂理解的深化

Scientists Ratchet Up Understanding of Cellular Protein Factory
科学家对于分子蛋白工厂的理解

ScienceDaily (Dec. 1, 2010) — Theoretical biologists at Los Alamos National Laboratory have used a New Mexico supercomputer to aid an international research team in untangling another mystery related to ribosomes -- those enigmatic jumbles of molecules that are the protein factories of living cells. The research, published December 2 in the journal Nature, could aid in development of new antibiotics used to fight multidrug resistant superbugs such as MRSA (methicillin-resistant Staphylococcus aureus infections) found in many U.S. hospitals. The work may also be important for combating engineered strains of anthrax and plague.
科学日报（2010年12月1日） - 在美国洛斯阿拉莫斯国家实验室的理论生物学家已经使用了新墨西哥州的超级计算机，以帮助一个国际研究小组解开有关核糖体另一个谜- 活细胞的蛋白质工厂分子神秘动力 。这项研究发表在12月2日的自然杂志上，可以有助于研发药针对美国许多医院中的对抗生素抗药的葡萄球菌（耐甲氧西林金黄色葡萄球菌感染）。这项工作也可用于防治炭疽工程菌和鼠疫。

In the context of synthetic biology, understanding the ribosome could be key to developing nanofactories that produce designer biomolecules and polymers.
在生物合成方面，了解核糖体是关键，发展纳米工厂来生产所设计的生物分子和聚合物。

In the paper, "Head swivel on the ribosome facilitates translocation via intra-subunit tRNA hybrid sites," Los Alamos National Laboratory researchers Karissa Sanbonmatsu and Paul Whitford and José N. Onuchic at the University of California-San Diego join Christian Spahn, Andreas Ratje, and others from the Institute for Medical Physics and Biophysics, Berlin, Germany, to describe for the first time how a complicated swivel movement within a bacterial ribosome accommodates synthesis of proteins.
在论文中，“头部旋转有利于通过内部核糖体亚基的tRNA移位”， 加州大学圣迭戈分校洛斯阿拉莫斯国家实验室的研究人员卡Karissa Sanbonmatsu 、 Paul Whitford 和 José N. Onuchic，其他来自柏林，德国医学物理学和生物物理学研究所，来形容首次如何在细菌核糖体进行复杂旋转运动来合成蛋白质。

Ribosomes are composed of long chemical chains, called ribonucleic acids (RNA), and proteins. Each ribosome has two interlocked subunits, one large and one small, which behave as a single molecular machine. Because of its makeup, each ribosome resembles a tangle of threads or a handful of rubber bands tossed together. Despite the ribosome's outwardly disjointed appearance, researchers have found that the two subunits ratchet, un-ratchet, and swivel during protein synthesis to allow introduction of helper chemicals called transfer RNAs (tRNAs) into its folds to manufacture new chains of protein molecules. The proteins are used to create new cells or perform necessary functions within the host cell or organism.
核糖体是由称为（RNA）的核糖核酸和蛋白质长化学链构成。每个亚基核糖体有两个相关的亚单位，一大一小，这表现为一个单一的分子机器。由于其构成，每个核糖体类似于一个线程缠结或一把橡皮筋捆在一起。尽管核糖体的表面上出现脱节，研究人员发现，这两个亚基有助于转运RNA（tRNA基因）来制造新的蛋白质分子链。这些蛋白质被用来制造新的细胞或在宿主细胞内或者生物体中执行必要的功能。

Ribosomes build proteins by linking chemical segments fashioned from instructions delivered via messenger RNA, which is DNA's molecular cousin. Each segment, or amino acid, corresponds to a trio of bases in the message that, in turn, complement trios encoded in transfer RNA. Each base in the trio corresponds to a single chemical complement found on the RNA. In order for protein synthesis to occur, the tRNA must bind to the ribosome at two distinct sites -- one to decode the information and another to link the new amino acid to the emerging protein.
核糖体从通过信使RNA将化学片段链接来制造蛋白，这是DNA的分子交付。每一部分，或氨基酸，对应于信使中的三个碱基，反过来，转运RNA编码的三个互补碱基。三人中的每个碱基都对应RNA上的一个化学成分。为了使蛋白质的合成，tRNA必须在两个不同位点结合到核糖体 - 一个解码信息，另一个连接新的氨基酸去合成新的蛋白质。

After each amino acid is added, the ribosome must crawl along the message to create additions. Exactly how this crawling occurs has been a mystery for several decades. Researchers have suspected that ratcheting motions of the two ribosomal subunits are key to allowing RNA and associated catalysts into the complex structure of the ribosome so the RNA and ribosome can couple at the crucial sites to create proteins. In the Nature paper, the researchers discovered that the majority of crawling (movement along messenger RNA) occurs during a new kind motion, "head swivel," rather than ratcheting.
每个氨基酸添加后，核糖体沿着信使去增加。移行如何进行的几十年来一直是个谜。研究人员推测，核糖体的两个亚基的运动是关键，如此是使RNA和催化酶进入核糖体的结构复杂，核糖体能在关键部位偶联来制造蛋白质。在《自然》的这篇论文中，研究者发现，多数移行（沿信使RNA运动）在一种新的运动中出现，“头部旋转”，而不是发生棘轮。

The paper describes how an antibiotic was used to inhibit the full swivel and ratcheting motion of a ribosome from a bacterium called Thermus Thermophilus, which thrives in hot acidic environments. The ribosomes were flash-frozen at various mid-swivel and mid-ratchet configurations and examined under a powerful electron microscope.
本文介绍了如何使用抗生素用在从嗜热栖热菌的细菌中抑制核糖体的棘轮充分旋转，在酸性环境中有明显活力。在高分辨率的电子显微镜下核糖体各种旋转棘轮中快速凝固。

The observed configurations were then coupled with a computer model newly developed at Los Alamos called MDFIT. The computer algorithm integrates molecular simulation with maps of ribosome structures obtained through the cryogenic microscopy. The Los Alamos team then used the Encanto supercomputer -- funded by the state of New Mexico and housed at the Intel plant in Rio Rancho -- to create molecular snapshots of the complicated motion of the ribosomal subunits during protein synthesis.
所观察到的配置，是在洛斯阿拉莫斯实验室新近开发出一种称为MDFIT的计算机模型耦合。计算机算法结合分子模拟图，通过低温显微镜获得核糖体的结构，。洛斯阿拉莫斯的球队然后用恩坎图超级计算机 - 由美国新墨西哥州资助，放置在里约牧场英特尔工厂 - 在蛋白质合成时来创建复杂的核糖体亚基分子的快照。

Previously, scientists were only able to observe the beginning or end states of the motion. These new images show the behavior of the ribosome through its range of motion -- much like early photographic motion studies that showed the entire fluid movement of a galloping horse. In addition to showing the importance of head swivel motion, the study showed that a key catalyst in the process acts as a dynamic pawl in the ribosomal machinery, providing directionality and acceleration for translocation of the tRNA. The understanding provided by the new model will help researchers to develop more effective antibiotics that target the ribosomal machinery of harmful organisms.
此前，科学家们只能观察运动的开始或结束状态。这些新的影像显示出核糖体的运动范围 - 就像早期照相运动研究资料，表明整个核糖体的运动。除了显示头部旋转运动的重要性，研究表明，在这个过程中的关键是催化剂作为一个动态的棘爪，提供了tRNA分子的易位方向性和加速度。由新模型提供的理解将有助于研究人员开发出更多有效的抗生素为来针对有害生物的核糖体。

"While static images of the ribosome have revealed the detailed structure of the complex, we still don't know how all the parts of the machine work together to make proteins," said Janna Wehrle, Ph.D., who oversees Dr. Sanbonmatsu's and other structural biology grants at the National Institutes of Health. "By showing how the bacterial ribosome carries out a key step of protein synthesis, this study has begun to produce a more dynamic picture while offering a new way to target harmful, multi-drug resistant bacteria."
“虽然核糖体的静态图像揭示了详细的复杂结构，我们仍然不知道如何让所有的机器工作部分组合在一起来制造使蛋白质，Janna Wehrle博士说，他是负责在美国国立卫生研究院Sanbonmatsu和其他结构生物学的资金的。 “通过展示细菌核糖体如何合成蛋白质的关键步骤，这项研究已开始产生更动态的画面，同时提供了一条新途径来针对具有多药抗药性的细菌。”

The research team includes: Andreas H. Ratje, Justus Loerke, Matthias Brünner, Peter W. Hildebrand, Thorsten Mielke and Christian M.T. Spahn, Institute of Medical Physics and Biophysics, Berlin; Aleksandra Mikolajka, Agata L. Starosta, Alexandra D?nh?fer and Daniel N. Wilson, Ludwig-Maximilians University, Munich; Sean R. Connell and Paola Fucini, Goeth University, Frankfurt; Paul C. Whitford and Karissa Y. Sanbonmatsu, Los Alamos National Laboratory, Los Alamos, New Mexico; José N. Onuchic, University of California-San Diego; Yanan Yu, Florida State University, Tallahassee, Florida; Roland K. Hartmann, Institute for Pharmaceutical Chemistry, Marburg, Germany; Pawel A. Penczek, University of Texas, Houston Medical School.
研究团队包括：柏林研究所医学物理学和生物物理学的Andreas H. Ratje, Justus Loerke, Matthias Brünner, Peter W. Hildebrand, Thorsten Mielke and Christian M.T. Spahn，Ludwig-Maximilians大学的Aleksandra Mikolajka, Agata L. Starosta, Alexandra D?nh?fer and Daniel N. Wilson，新墨西哥洛斯阿拉莫斯国家实验室的Sean R. Connell and Paola Fucini, Goeth University, Frankfurt; Paul C. Whitford and Karissa Y. Sanbonmatsu, Los Alamos National Laboratory, Los Alamos, New Mexico，美国佛罗里达州立大学的José N. Onuchic，佛罗里达州的Yanan Yu，
德国制药化学研究所的Roland K. Hartmann，德克萨斯大学休斯顿医学院的Pawel A. Penczek。