Synthesis of High Titer Infectious Prions with Cofactor Molecules [Protein Structure and Folding]

May 23rd, 2014 by Supattapone, S.

Recently, synthetic prions with a high level of specific infectivity have been produced from chemically defined components in vitro. A major insight arising from these studies is that various classes of host-encoded cofactor molecules such as phosphatidylethanolamine (PE) and RNA molecules are required to form and maintain the specific conformation of infectious prions. Synthetic prions formed with cofactors exhibit levels of specific infectivity ~ 1 million-fold greater than protein only prions. Moreover, cofactor molecules also appear to regulate prion strain properties by limiting the potential conformations of the prion protein. The production of fully infectious synthetic prions provides new opportunities to study the mechanism of prion infectivity directly by structural and biochemical methods.