Surface Features of Prions Reveal Mechanism of Replication
Sporadic human prion diseases are conceivably the most heterogenous neurodegenerative disorders and a growing body of research indicates that they are caused by distinct strains of prions.
Using parallel monitoring of prion replication potency and progressive hydroxyl radical modification of amino acid side chains during synchrotron irradiation, researchers identified major differences in the structural organization of human prion strains that correlate with distinct inactivation susceptibility. Furthermore, the data demonstrated that the seeding activity of different strains of infectious brain-derived human prions is primarily a function of distinct solvent-exposed structural domains. The structural domains are implicated in the initial binding of cellular isoform of prion protein (PrPC) as a critical step in human prion replication and infectivity.
Siddiqi MK, Kim C, Haldiman T, Kacirova M, Wang B, Bohon J, et al. (2021) “Structurally distinct external solvent-exposed domains drive replication of major human prions.” PLoS Pathog 17(6): e1009642. [DOI: 10.1371/journal.ppat.1009642]