Novel quaternary structures of the human prion protein globular domain.

ABSTRACT: Prion disease is caused by the misfolding of the cellular prion protein, PrP^C, into a self-templating conformer, PrP^Sc. Nuclear magnetic resonance (NMR) and X-ray crystallography revealed the 3D structure of the globular domain of PrP^C and the possibility of its dimerization via an interchain disulfide bridge that forms due to domain swap or by non-covalent association of two monomers. On the contrary, PrP^Sc is composed by a complex and heterogeneous ensemble of poorly defined conformations and quaternary arrangements that are related to different patterns of neurotoxicity. Targeting PrP^C with molecules that stabilize the native conformation of its globular domain emerged as a promising approach to develop anti-prion therapies. One of

SUBMITTER: Bortot LO 

PROVIDER: S-EPMC8627497 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature