99 — The Structural Architecture of an Infectious Mammalian Prion Using Electron Cryomicroscopy

PrP^Sc is a misfolded “prion” protein responsible for Creutzfeldt-Jakob diease much like mad cow or scrapie.

This protein continues to evade close study: It’s known that the endogenous form, PrP^C, is produced by the body, but the prion form converts healthy proteins into misfolded onces. This diseased state is fatal and unreversible.

Using the crystal structure of the biological prion aggregates, Vázquez-Fernández et al were able to determine a bounding box for the size and dimensions of the prion protein. They also performed 3D reconstructions that indicated that the structure contained a four-rung $\Beta$ solenoid.

THe author summary contains the bold statement that “the data conflict with all previous models for the structure of PrP^Sc,” which is always a sign of an exciting paper.

The paper demonstrates the resultant data from the cryomicroscopy scans: The protein under study appears to have a helix shape, which looks an awful lot like a Twizzler (especially in the candy-red color they’ve used in their diagrams).

This work is exciting because it begins to shed more light on the nature of prionopathies, which are notoriously difficult to study. (CJD is very rare in humans, and it’s unknown how best to emulate the disease faithfully in a model).