Department of Anatomy, Physiology, Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Int J Mol Sci. 2020 Sep 25;21(19):7058. doi: 10.3390/ijms21197058.
Cellular prion protein (PrPc) is a small glycosylphosphatidylinositol (GPI) anchored protein most abundantly found in the outer leaflet of the plasma membrane (PM) in the central nervous system (CNS). PrPc misfolding causes neurodegenerative prion diseases in the CNS. PrPc interacts with a wide range of protein partners because of the intrinsically disordered nature of the protein's N-terminus. Numerous studies have attempted to decipher the physiological role of the prion protein by searching for proteins which interact with PrPc. Biochemical characteristics and biological functions both appear to be affected by interacting protein partners. The key challenge in identifying a potential interacting partner is to demonstrate that binding to a specific ligand is necessary for cellular physiological function or malfunction. In this review, we have summarized the intracellular and extracellular interacting partners of PrPc and potential consequences of their binding. We also briefly describe prion disease-related mutations at the end of this review.
细胞朊蛋白(PrPc)是一种小的糖基磷脂酰肌醇(GPI)锚定蛋白,在中枢神经系统(CNS)的质膜(PM)的外叶中含量最丰富。PrPc 的错误折叠导致 CNS 中的神经退行性朊病毒病。由于蛋白质的 N 端具有固有无序的性质,PrPc 与广泛的蛋白质伴侣相互作用。许多研究试图通过寻找与 PrPc 相互作用的蛋白质来破译朊病毒蛋白的生理作用。生化特性和生物学功能似乎都受到相互作用的蛋白质伴侣的影响。鉴定潜在相互作用伙伴的关键挑战是证明与特定配体的结合对于细胞生理功能或功能障碍是必要的。在这篇综述中,我们总结了 PrPc 的细胞内和细胞外相互作用伙伴及其结合的潜在后果。在这篇综述的结尾,我们还简要描述了朊病毒病相关的突变。