Aebersold_MSB_微生物不同形態下蛋白質組的絕對定量

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 identi?ed from a sample and the relative abundance of the identi?ed 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 ?rst 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.

通過測量蛋白版本數量進行的絕對蛋白定量分析，有可能為生物學過程提供重要信息，但除了釀酒酵母的特例外，此前利用標準蛋白質組軟件尚未證明這種可能性。

現在，以鉤端螺旋體病病原體“腎臟鉤端螺旋體”作為第一個目標，一種新的質譜方法被用來確定一個蛋白質組體系中相當大一部分的絕對蛋白質豐度，而該方法所依據的策略應可普遍應用于很多其他的生物學體系。該研究的結果反映了“腎臟鉤端螺旋體”是怎樣在總蛋白拷貝數量保持不變的情況下，通過調整蛋白質組的動態平衡來適應環境變化的。

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