Markley John L, Aceti David J, Bingman Craig A, Fox Brian G, Frederick Ronnie O, Makino Shin-ichi, Nichols Karl W, Phillips George N, Primm John G, Sahu Sarata C, Vojtik Frank C, Volkman Brian F, Wrobel Russell L, Zolnai Zsolt
Center for Eukaryotic Structural Genomics, Biochemistry Department, University of Wisconsin-Madison, Madison, WI 53706, USA.
J Struct Funct Genomics. 2009 Apr;10(2):165-79. doi: 10.1007/s10969-008-9057-4. Epub 2009 Jan 8.
The Center for Eukaryotic Structural Genomics (CESG) is a "specialized" or "technology development" center supported by the Protein Structure Initiative (PSI). CESG's mission is to develop improved methods for the high-throughput solution of structures from eukaryotic proteins, with a very strong weighting toward human proteins of biomedical relevance. During the first three years of PSI-2, CESG selected targets representing 601 proteins from Homo sapiens, 33 from mouse, 10 from rat, 139 from Galdieria sulphuraria, 35 from Arabidopsis thaliana, 96 from Cyanidioschyzon merolae, 80 from Plasmodium falciparum, 24 from yeast, and about 25 from other eukaryotes. Notably, 30% of all structures of human proteins solved by the PSI Centers were determined at CESG. Whereas eukaryotic proteins generally are considered to be much more challenging targets than prokaryotic proteins, the technology now in place at CESG yields success rates that are comparable to those of the large production centers that work primarily on prokaryotic proteins. We describe here the technological innovations that underlie CESG's platforms for bioinformatics and laboratory information management, target selection, protein production, and structure determination by X-ray crystallography or NMR spectroscopy.
真核生物结构基因组学中心(CESG)是由蛋白质结构计划(PSI)支持的一个“专门”或“技术开发”中心。CESG的任务是开发改进的方法,用于高通量解析真核生物蛋白质的结构,特别侧重于具有生物医学相关性的人类蛋白质。在PSI-2的前三年中,CESG选择的目标代表了来自智人的601种蛋白质、来自小鼠的33种、来自大鼠的10种、来自嗜热栖热放线菌的139种、来自拟南芥的35种、来自梅氏隐球酵母的96种、来自恶性疟原虫的80种、来自酵母的24种,以及来自其他真核生物的约25种。值得注意的是,PSI各中心解析的所有人类蛋白质结构中,有30%是在CESG确定的。虽然一般认为真核生物蛋白质比原核生物蛋白质更具挑战性,但CESG目前采用的技术所产生的成功率与主要处理原核生物蛋白质的大型生产中心相当。我们在此描述构成CESG生物信息学和实验室信息管理、目标选择、蛋白质生产以及通过X射线晶体学或核磁共振光谱进行结构测定平台基础的技术创新。