**Carolina Sánchez-López 1,†, Giulia Rossetti 2,3,4, Liliana Quintanar 1,\* and Paolo Carloni 2,5,6,\***


Received: 3 December 2018; Accepted: 18 December 2018; Published: 20 December 2018

**Abstract:** The N-terminus of the prion protein is a large intrinsically disordered region encompassing approximately 125 amino acids. In this paper, we review its structural and functional properties, with a particular emphasis on its binding to copper ions. The latter is exploited by the region's conformational flexibility to yield a variety of biological functions. Disease-linked mutations and proteolytic processing of the protein can impact its copper-binding properties, with important structural and functional implications, both in health and disease progression.

**Keywords:** N-terminal prion protein; copper binding; prion disease mutations
