AI Article Synopsis
- Prion diseases are deadly and incurable neurodegenerative disorders caused by misfolded prion proteins, affecting both humans and animals.
- A specific mutation (G127V) in the human prion protein (PrP) has been found to prevent these diseases, but the precise structural changes responsible for this protective effect were not previously understood.
- The study reveals that this mutation stabilizes interactions between PrP molecules and alters the dynamics of a key region involved in prion transmission, potentially reducing the likelihood of prion formation and offering insight into its role in preventing prion diseases.
Article Abstract
Prion diseases, a group of incurable, lethal neurodegenerative disorders of mammals including humans, are caused by prions, assemblies of misfolded host prion protein (PrP). A single point mutation (G127V) in human PrP prevents prion disease, however the structural basis for its protective effect remains unknown. Here we show that the mutation alters and constrains the PrP backbone conformation preceding the PrP β-sheet, stabilising PrP dimer interactions by increasing intermolecular hydrogen bonding. It also markedly changes the solution dynamics of the β2-α2 loop, a region of PrP structure implicated in prion transmission and cross-species susceptibility. Both of these structural changes may affect access to protein conformers susceptible to prion formation and explain its profound effect on prion disease.
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Source |
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391680 | PMC |
| http://dx.doi.org/10.1038/s42003-020-01126-6 | DOI Listing |
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