The prion protein and its ligands: Insights into structure-function relationships

The prion protein is a multifunctional protein that exists in at least two different folding states. It is subject to diverse proteolytic processing steps that lead to prion protein fragments some of which are membrane-bound whereas others are soluble. A multitude of ligands bind to the prion protein and besides proteinaceous binding partners, interaction with metal ions and nucleic acids occurs. Although of great importance, information on structural and functional consequences of prion protein binding to its partners is limited. Here, we will reflect on the structure-function relationship of the prion protein and its binding partners considering the different folding states and prion protein fragments. •PrPC is a multifunctional glycoprotein, highly expressed in nervous and immune tissues.•Variety of ligands binding to PrPC partly contribute to its functional diversity.•Current review provides a note on PrPC ligands and resulting biological effects.