Prion proteins are "misfolded"and cause a group of incurable neurodegenerative diseases, including spongiform encephalopathies (for example, mad cow diseases) and Creutzfeldt-Jakob disease. 

Prions are unique infective agents. Unlike viruses, bacteria, fungi and other parasites, prions do not contain either DNA or RNA. Despite their seemingly simple structure, they can propagate their pathological effects like wildfire, by "infecting" normal proteins.

PrPSc (the pathological form of the prion protein) can induce normal prion proteins (PrPC) to acquire the wrong conformation and convert into further disease-causing agents. 

"When they are healthy, they look like tiny spheres; when they are malignant, they appear as cubes," says Giuseppe Legname, principal investigator of the Prion Biology Laboratory at the Scuola Internazionale Superiore di Studi Avanzati (SISSA) in Trieste. Legname and colleagues have recently published a detailed analysis of the early mechanisms of misfolding.

"For the first time, our experimental study has investigated the structural elements leading to the disease-causing conversion" explains Legname. "With the help of X-rays, we observed some synthetic prion proteins engineered in our lab by applying a new approach —we used nanobodies, i.e. small proteins that act as a scaffolding and induce prions to stabilize their structure".

They reported that misfolding originates in a specific part of the protein named "N-terminal".

 "The prion protein consists of two subunits. The C-terminal has a clearly defined and well-known structure, whereas the unstructured N-terminal is disordered, and still largely unknown. This is the very area where the early prion pathological misfolding occurs" stated Legname. "The looser conformation of the N-terminal likely determines a dynamic structure, which can thus change the protein shape."