Charting colorectal cancer Interactomes at structural resolution using chemical crosslinking and mass spectrometry

通过基因组学已经发现了大量的癌症突变；然而，目前还不清楚大多数癌症基因是如何发挥作用并对疾病过程产生影响的。在这里，我们建议开发一种使用交联质谱(XL-MS)在全球范围内高通量地绘制蛋白质相互作用图的定量方法。该方法将用于绘制跨癌细胞系的天然蛋白质相互作用图景，生成关于蛋白质拓扑和蛋白质-蛋白质相互作用(PPI)表面的结构信息。更深入地了解体细胞突变如何影响蛋白质结构、功能和细胞网络的重新布线，将提供机械性的见解，并支持新的干预策略。

Large numbers of cancer mutations have been exposed through genomics; however, it remains unclear how most cancer genes function and exert influence on disease processes. Here we propose to develop a quantitative approach to map protein interactions on global scale at high throughput using cross-linking mass spectrometry (XL-MS). The method will be used to chart the native protein interaction landscapes across cancer cell lines, generating structural information on protein topology and protein-protein interaction (PPI) surfaces. A deeper understanding of how somatic mutations affect protein structure, function and rewiring of cellular networks, will provide mechanistic insights and underpins new intervention strategies.