Notch信号通路在后生动物物种中进化保守，并且在很多生理过程中发挥着重要作用。Notch受体由两个典型的配体家族（Delta和Serrate/Jagged）激活，其中配体和受体都是单向跨膜蛋白，相对于其细胞内部分，它们通常有较大的胞外结构域。当存在相对细胞面上的核心结合区域发生相互作用时，受体/配体络合物的形成会引发力介导的蛋白水解作用，最终释放出具有转录活性的Notch胞内结构域。本文重点关注细胞外受体/配体络合物的结构特点、翻译后修饰对调节该络合物所发挥的作用、细胞膜对配体功能的贡献，以及对获得性和遗传性疾病的见解。

The Notch signaling pathway is evolutionarily conserved across metazoan species and plays key roles in many physiological processes. The Notch receptor is activated by two families of canonical ligands (Delta-like and Serrate/Jagged) where both ligands and receptors are single-pass transmembrane proteins usually with large extracellular domains, relative to their intracellular portions. Upon interaction of the core binding regions, presented on opposing cell surfaces, formation of the receptor/ligand complex initiates force-mediated proteolysis, ultimately releasing the transcriptionally-active Notch intracellular domain. This review focuses on structural features of the extracellular receptor/ligand complex, the role of post-translational modifications in tuning this complex, the contribution of the cell membrane to ligand function, and insights from acquired and genetic diseases.