Open AccessThe protean prion protein
Author(s) -
Jesús R. Requena
Publication year - 2020
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3000754
Subject(s) - scrapie , neurodegeneration , biology , prion protein , infectious agent , amyloid (mycology) , conformational isomerism , protein structure , biophysics , microbiology and biotechnology , chemistry , biochemistry , disease , molecule , medicine , botany , organic chemistry , pathology
The prion protein, PrP, can adopt at least 2 conformations, the overwhelmingly prevalent cellular conformation (PrP C ) and the scrapie conformation (PrP Sc ). PrP C features a globular C-terminal domain containing 3 α-helices and a short β-sheet and a long flexible N-terminal tail whose exact conformation in vivo is not yet known and a metastable subdomain with β-strand propensity has been identified within it. The PrP Sc conformation is very rare and has the characteristics of an amyloid. Furthermore, PrP Sc is a prion, i.e., it is infectious. This involves 2 steps: (1) PrP Sc can template PrP C and coerce it to adopt the PrP Sc conformation and (2) PrP Sc can be transmitted between individuals, by oral, parenteral, and other routes and thus propagate as an infectious agent. However, this is a simplification: On the one hand, PrP Sc is not a single conformation, but rather, a set of alternative similar but distinct conformations. Furthermore, other amyloid conformations of PrP exist with different biochemical and propagative properties. In this issue of PLOS Biology , Asante and colleagues describe the first murine model of familial human prion disease and demonstrate the emergence and propagation of 2 PrP amyloid conformers. Of these, one causes neurodegeneration, whereas the other does not. With its many conformers, PrP is a truly protean protein.