Price W Nicholson, Chen Yang, Handelman Samuel K, Neely Helen, Manor Philip, Karlin Richard, Nair Rajesh, Liu Jinfeng, Baran Michael, Everett John, Tong Saichiu N, Forouhar Farhad, Swaminathan Swarup S, Acton Thomas, Xiao Rong, Luft Joseph R, Lauricella Angela, DeTitta George T, Rost Burkhard, Montelione Gaetano T, Hunt John F
Northeast Structural Genomics Consortium, Columbia University, New York, New York 10027, USA.
Nat Biotechnol. 2009 Jan;27(1):51-7. doi: 10.1038/nbt.1514.
Crystallization is the most serious bottleneck in high-throughput protein-structure determination by diffraction methods. We have used data mining of the large-scale experimental results of the Northeast Structural Genomics Consortium and experimental folding studies to characterize the biophysical properties that control protein crystallization. This analysis leads to the conclusion that crystallization propensity depends primarily on the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. We identify specific sequence features that correlate with crystallization propensity and that can be used to estimate the crystallization probability of a given construct. Analyses of entire predicted proteomes demonstrate substantial differences in the amino acid-sequence properties of human versus eubacterial proteins, which likely reflect differences in biophysical properties, including crystallization propensity. Our thermodynamic measurements do not generally support previous claims regarding correlations between sequence properties and protein stability.
结晶是通过衍射方法进行高通量蛋白质结构测定中最严重的瓶颈。我们利用东北结构基因组学联盟的大规模实验结果进行数据挖掘以及实验性折叠研究，来表征控制蛋白质结晶的生物物理特性。该分析得出的结论是，结晶倾向主要取决于能够介导蛋白质间相互作用的有序表面表位的普遍性，而不受整体热力学稳定性的强烈影响。我们确定了与结晶倾向相关且可用于估计给定构建体结晶概率的特定序列特征。对整个预测蛋白质组的分析表明，人类蛋白质与真细菌蛋白质的氨基酸序列特性存在显著差异，这可能反映了包括结晶倾向在内的生物物理特性的差异。我们的热力学测量结果一般不支持先前关于序列特性与蛋白质稳定性之间相关性的说法。
