Copper coordination modulates prion conversion and infectivity in mammalian prion proteins

In mammals the cellular form of the prion protein (PrPC) is a ubiquitous protein involved in many relevant functions in the central nervous system. In addition to its physiological functions PrPC plays a central role in a group of invariably fatal neurodegenerative disorders collectively called prion diseases. In fact, the protein is a substrate in a process in which it converts into an infectious and pathological form denoted as prion. The protein has a unique primary structure where the unstructured N-terminal moiety possesses characteristic sequences wherein histidines are able to coordinate metal ions, in particular copper ions. These sequences are called octarepeats for their characteristic length. Moreover, a non-octarepeat fifth-copper binding site is present where copper coordination seems to control infectivity. In this review, I will argue that these sequences may play a significant role in modulating prion conversion and replication.

Automated summary

In mammals, the prion protein (PrPC) is a common protein involved in various functions in the central nervous system. It also plays a central role in prion diseases, a group of fatal neurodegenerative disorders. The protein can convert into an infectious form called prion and its unique structure, including octarepeat sequences and copper binding sites, may modulate prion conversion and replication.