Abstract:
Structural information on protein-protein interactions (PPIs) is essential for improved understanding of regulatory interactome networks that confer various physiological and pathological responses. Additionally, maladaptive PPIs constitute desirable therapeutic targets due to inherently high disease state specificity. Recent advances in chemical cross-linking strategies coupled with mass spectrometry (XL-MS) have positioned XL-MS as a promising technology to not only elucidate the molecular architecture of individual protein assemblies, but also to characterize proteome-wide PPI networks. Moreover, quantitative in vivo XL-MS provides a new capability for the visualization of cellular interactome dynamics elicited by drug treatments, disease states, or aging effects. The emerging field of XL-MS based complexomics enables unique insights on protein moonlighting and protein complex remodeling. These techniques provide complimentary information necessary for in-depth structural interactome studies to better comprehend how PPIs mediate function in living systems.
摘要:
蛋白质-蛋白质相互作用(PPIs)的结构信息对于改善对赋予各种生理和病理反应的调节相互作用网络的理解至关重要。此外,由于固有的高疾病状态特异性,适应性不良的PPI构成了理想的治疗靶标。化学交联策略与质谱联用(XL-MS)的最新进展已将XL-MS定位为一种有前途的技术,不仅可以阐明单个蛋白质组装体的分子结构,还可以表征蛋白质组范围的PPI网络。此外,定量体内XL-MS为药物治疗引起的细胞相互作用动力学的可视化提供了新的能力,疾病状态,或老化的影响。基于XL-MS的复合物组学的新兴领域使人们对蛋白质月光和蛋白质复合物重塑具有独特的见解。这些技术为深入的结构相互作用组研究提供了必要的补充信息,以更好地理解PPI如何介导生命系统中的功能。