Seminar

The structure of PrPSc in search of the 'double helix' of prions

Jesús Rodríguez Requena, PhD

Prions are infectious proteins that transmit deadly neurodegenerative diseases. More broadly, prions are proteins that store and transmit information, a property previously thought to be exclusive of nucleic acids. Prion-like information transmission might be more common than thought, and might play a role in key biological processes such as self/non-self recognition, memory, and amyloid diseases in general. But how do prions work? They store information conformationally: all known prions are amyloids, and it is conceivable that their "information code" consists of non-covalent bonds between amino acids not unlike base-pairing in nucleic acids. Just as the mechanism of nucleic acid-based transmission of information was immediately obvious once the structure of DNA was solved, solving the structure of prions will lead to an understanding of how they work. However, deciphering the structure of prions is not an easy task, given their aggregated, insoluble nature. Some tantalizing data based on cryo-electron tomography and microscopy, and biochemical approaches will be presented. Structural data from several groups, including ours, is beginning to reveal the code of protein-based information transmission.