Aebersold_MSB_微生物不同形态下蛋白质组的绝对定量

Molecular Systems Biology
www.molecularsystemsbiology.com
 Ruedi Aebersold


Over the past decade, liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) has evolved into the main proteome discovery technology. Up to several thousand proteins can now be reliably identified from a sample and the relative abundance of the identified proteins can be determined across samples. However, the remeasurement of substantially similar proteomes, for example those generated by perturbation experiments in systems biology, at high reproducibility and throughput remains challenging. Here, we apply a directed MS strategy to detect and quantify sets  of  pre-determined  peptides  in  tryptic  digests  of  cells  of  the  human  pathogen  Leptospira interrogans at 25 different states. We show that in a single LC–MS/MS experiment around 5000 peptides, covering 1680 L. interrogans proteins, can be consistently detected and their absolute expression  levels  estimated,  revealing  new  insights  about  the  proteome  changes  involved  in pathogenic progression and antibiotic defense of L. interrogans. This is the first study that describes the absolute quantitative behavior. of any proteome over multiple states, and represents the most comprehensive proteome abundance pattern comparison for any organism to date.

通过测量蛋白版本数量进行的绝对蛋白定量分析，有可能为生物学过程提供重要信息，但除了酿酒酵母的特例外，此前利用标准蛋白质组软件尚未证明这种可能性。

现在，以钩端螺旋体病病原体“肾脏钩端螺旋体”作为第一个目标，一种新的质谱方法被用来确定一个蛋白质组体系中相当大一部分的绝对蛋白质丰度，而该方法所依据的策略应可普遍应用于很多其他的生物学体系。该研究的结果反映了“肾脏钩端螺旋体”是怎样在总蛋白拷贝数量保持不变的情况下，通过调整蛋白质组的动态平衡来适应环境变化的。

http://www.nature.com/msb/journal/v7/n1/full/msb201137.html