PRNP

PRNP Full Name

prion protein

PRNP Introduction

The prion protein (PrP) is a naturally occurring, cell-surface glycoprotein found primarily in neurons. Its abnormal, misfolded isoform, known as the "scrapie form" , is the unique infectious agent responsible for a group of fatal, transmissible neurodegenerative diseases called transmissible spongiform encephalopathies (TSEs) or prion diseases. Unlike all other known pathogens (viruses, bacteria, fungi), prions lack nucleic acid and propagate solely by inducing the conformational change of the normal cellular prion protein into the pathological form.

Figure 1. Cartoon representation of the secondary prion protein structure.(Source: Salzano, G, 2019)

Cellular Prion Protein (PrP)
The cellular prion protein (PrP) is a host-encoded, non-pathogenic protein expressed in most mammalian cell types, with particularly high levels in the central nervous system (CNS). Encoded by the PRNP gene (located on chromosome 20 in humans and chromosome 2 in mice), PrP undergoes post-translational modifications, including glycosylation and attachment of a glycosylphosphatidylinositol (GPI) anchor that tethers it to the outer leaflet of the cell membrane. Structurally, PrP features a flexible, intrinsically disordered N-terminal domain and a globular C-terminal domain. The C-terminal domain contains three α-helices, two short antiparallel β-strands, and a disulfide bridge, which stabilize its native conformation. The N-terminal domain includes octarepeat motifs (consensus sequence: PHGGGWGQ) that bind divalent cations such as copper ions (Cu), a property linked to its physiological functions.

Conclusion
Prion proteins represent a unique class of pathogenic agents, challenging traditional notions of infectivity by relying solely on protein conformation rather than nucleic acid. Their ability to induce fatal neurodegeneration has spurred decades of research into their structure, function, and pathogenic mechanisms. While no cures exist for prion diseases, advances in gene therapy and mechanistic understanding hold promise for future interventions. Moreover, prion research illuminates broader principles of protein homeostasis and neurodegeneration, with implications for treating a range of devastating neurological disorders.

Alternate Names for PRNP

PRNP; prion protein; CJD; GSS; PrP; ASCR; KURU; PRIP; PrPc; CD230; AltPrP; p27-30; PrP27-30; PrP33-35C; major prion protein; CD230 antigen; prion-related protein;

• 1.Salzano, G., Giachin, G., & Legname, G. . Structural consequences of copper binding to the prion protein. Cells, 2019, 8(8), 770.