Post-translational modifications, complex formation, subcellular localization, and cell-type-specific expression create functionally distinct protein subpopulations that enable living systems to execute rapid and precise responses to changing conditions. Systems-level analysis of these subproteomes remains challenging, requiring preservation of spatial information or enrichment of species that are transient and present at low abundance. Engineered proteins have emerged as important tools for selective proteomics based on their capacity for highly specific molecular recognition and their genetic targetability. Here, we focus on new developments in protein engineering for selective proteomics of post-translational modifications, protein complexes, subcellular compartments, and cell types. We also address remaining challenges and future opportunities to integrate engineered protein tools across different subproteome scales to map the proteome with unprecedented depth and detail.

翻译后修饰、复合物形成、亚细胞定位和细胞类型特异性表达创造了功能不同的蛋白质亚群，使生命系统能够对不断变化的条件做出快速而精确的反应。这些亚蛋白质组的系统级分析仍然具有挑战性，需要保存空间信息或富集暂时且低丰度的物种。基于其高度特异性分子识别能力和遗传靶向性，工程蛋白已成为选择性蛋白质组学的重要工具。在这里，我们专注于蛋白质工程的新发展，用于翻译后修饰、蛋白质复合物、亚细胞区室和细胞类型的选择性蛋白质组学。