一组由多所研究机构组成的课题小组首次成功地对海栖热袍菌(T. maritima)的蛋白质三维结构和主要代谢网络建立了一个完整的模型。对该模型的分析表明,着重强调一少部分的重要蛋白质的结构,将加深对蛋白质网络的演变以及该蛋白质网络的功能的了解。这些研究报告发表在9月18日的Science杂志上。
该课题组结合了生物化学研究,结构基因组学和计算机模型等学科知识,成功破译了海栖热袍菌的主要代谢过程中478个蛋白质的形状,功能以及这些蛋白之间的相互作用。而且,研究人员还发现了这些蛋白质以及562种细胞内代谢反应和83种细胞外代谢反应之间的联系。
此外,令研究人员感到惊奇的是,该网络结构中蛋白质的保守程度——在478种蛋白质的714个结构域中,仅有182种不同的折叠方式,该发现验证了,自然界可以利用已存在的形状,略加修改后可以应用于新的任务中的假说。
利用这些数据,科学家在生化和分子水平上同时模拟这些代谢反应。而且,该研究中所建立的各种网络关系还可以应用到其他许多生物的研究中,包括人类研究。(生物谷Bioon.com)
生物谷推荐原始出处:
Science 18 September 2009:DOI: 10.1126/science.1174671
Three-Dimensional Structural View of the Central Metabolic Network of Thermotoga maritima
Ying Zhang,1,* Ines Thiele,2,*, Dana Weekes,3 Zhanwen Li,1 Lukasz Jaroszewski,3 Krzysztof Ginalski,4 Ashley M. Deacon,5 John Wooley,6 Scott A. Lesley,7 Ian A. Wilson,8 Bernhard Palsson,2 Andrei Osterman,9 Adam Godzik1,3,6,
Metabolic pathways have traditionally been described in terms of biochemical reactions and metabolites. With the use of structural genomics and systems biology, we generated a three-dimensional reconstruction of the central metabolic network of the bacterium Thermotoga maritima. The network encompassed 478 proteins, of which 120 were determined by experiment and 358 were modeled. Structural analysis revealed that proteins forming the network are dominated by a small number (only 182) of basic shapes (folds) performing diverse but mostly related functions. Most of these folds are already present in the essential core (~30%) of the network, and its expansion by nonessential proteins is achieved with relatively few additional folds. Thus, integration of structural data with networks analysis generates insight into the function, mechanism, and evolution of biological networks.
1 Joint Center for Molecular Modeling (JCMM), Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
2 Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093–0412, USA.
3 Joint Center for Structural Genomics (JCSG), Bioinformatics Core, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
4 Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, Warsaw, Poland.
5 JCSG, Structure Determination Core, Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA.
6 JCSG, Bioinformatics Core, University of California at San Diego, La Jolla, CA 92093, USA.
7 JCSG, Crystallomics Core, Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
8 JCSG, The Scripps Research Institute, La Jolla, CA 92037, USA.
9 Burnham Institute for Medical Research, La Jolla, CA 92037, USA.