The identification of individual protein-protein interactions (PPIs) began more than 40 years ago, using protein affinity chromatography and antibody co-immunoprecipitation. As new technologies emerged, analysis of PPIs increased to a genome-wide scale with the introduction of intracellular tagging methods, affinity purification (AP) followed by mass spectrometry (MS), and co-fractionation MS (CF-MS). Now, combining the resulting catalogs of interactions with complementary methods, including crosslinking MS (XL-MS) and cryogenic electron microscopy (cryo-EM), helps distinguish direct interactions from indirect ones within the same or between different protein complexes. These powerful approaches and the promise of artificial intelligence applications like AlphaFold herald a future where PPIs and protein complexes, including energy-driven protein machines, will be understood in exquisite detail, unlocking new insights in the contexts of both basic biology and disease.

中文翻译：

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蛋白质-蛋白质相互作用在健康和疾病中的发现和意义


个体蛋白质-蛋白质相互作用 （PPI） 的鉴定始于 40 多年前，使用蛋白质亲和层析和抗体免疫共沉淀。随着新技术的出现，随着细胞内标记方法、亲和纯化 （AP） 后质谱 （MS） 和共组分分离 MS （CF-MS） 的引入，PPI 的分析增加到全基因组规模。现在，将所得的相互作用目录与互补方法相结合，包括交联 MS （XL-MS） 和低温电子显微镜 （cryo-EM），有助于区分相同或不同蛋白质复合物内的直接相互作用和间接相互作用。这些强大的方法和 AlphaFold 等人工智能应用的承诺预示着未来，PPI 和蛋白质复合物（包括能量驱动的蛋白质机器）将被详细理解，从而在基础生物学和疾病的背景下解锁新的见解。