Hosszu LLP, Conners R, Sangar D, Batchelor M, Sawyer EB, Fisher S, Cliff MJ, Hounslow AM, McAuley K, Leo Brady R, Jackson GS, Bieschke J, Waltho JP and Collinge J 2020. Structural effects of the highly protective V127 polymorphism on human prion protein. Communications Biology. 3 402. https://doi.org/10.1038/s42003-020-01126-6
| Title | Structural effects of the highly protective V127 polymorphism on human prion protein. |
|---|---|
| Type | Journal article |
| Authors | Hosszu LLP, Conners R, Sangar D, Batchelor M, Sawyer EB, Fisher S, Cliff MJ, Hounslow AM, McAuley K, Leo Brady R, Jackson GS, Bieschke J, Waltho JP and Collinge J |
| 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. |
| Article number | 402 |
| Journal | Communications Biology |
| Journal citation | 3 |
| ISSN | 2399-3642 |
| Year | 2020 |
| Publisher | Nature Publishing Group |
| Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
| Digital Object Identifier (DOI) | https://doi.org/10.1038/s42003-020-01126-6 |
| PubMed ID | 32728168 |
| Web address (URL) | http://europepmc.org/abstract/med/32728168 |
| Publication dates | |
| Published | 29 Jul 2020 |