Researchers discover the mechanism that changes prions from "good" to "bad".

Prions are responsible for several neurodegenerative diseases such as Creutzfeld-Jakob's and "mad cow" disease. Moreover, prions are also infectious, since they can be transmitted between humans and even between species.

The PrPC protein constitutes the non-pathogenic form of prions, and is involved in many normal physiological processes. This non-pathogenic state has a mainly helical form. However, this protein can change its shape through some mechanisms, acquiring pathogenic characteristics that threaten humans as well as animals.

PrPC structure in its non-pathogenic form in humans. See in PDB.

According to a new study from the International School for Advanced Studies (SISSA), the mechanism responsible for this change is a metal, copper; specifically, a region in the protein which copper can bind to, which would trigger the change of PrPC into a harmful prion.

"We still don't know what complex molecular mechanisms cuse the prion protein to become bad", explains Giuseppe Legname, professor at SISSA. "Nor do we know any treatments to cure prion diseases. Our research has finally uncovered a critical factor, which is capable of triggering the transformation of prion proteins from good to bad".

Conformational change the PrPC protein suffers in its transition to a pathogenic form due to ineffective copper binding. Credit: SISSA.

According to Legname, copper binds strongly to two of the amino acids that make up the protein; specifically histidine. This union is good because it "protects" the prion protein. If copper is missing, or if it binds to one histidine instead of two, the prion protein turns unstable and becomes infectious.

Source: http://www.eurekalert.org/pub_releases/2015-10/isoa-fgt101915.php