The conversion to a disease-associated conformer (PrP (Sc) ) of the cellular prion protein (PrP (C) ) is the central event in prion diseases. Wild-type PrPC converts to PrP (Sc) in the sporadic forms of the disorders through an unknown mechanism. These forms account for up to 85% of all human (Hu) occurrences; the infectious types contribute for less than 1%, while genetic incidence of the disease is about 15%. Familial Hu prion diseases are associated with about forty point mutations of the gene coding for the PrP denominated PRNP. Most of the variants associated with these mutations are located in the globular domain of the protein. In a recent work in collaboration with the German Research School for Simulation Science, in Jülich, Germany, we performed molecular dynamics simulations for each of these mutants to investigate their structure in aqueous solution. Structural analysis of the various point mutations present in the globular domain unveiled common folding traits that may allow to a better understanding of the early conformational changes leading to the formation of monomeric PrP (Sc) . Recent experimental data support these findings, thus opening novel approaches to determine initial structural determinants of prion formation. © 2012 Landes Bioscience.
|Titolo:||Early structural features in mammalian prion conformation conversion|
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||10.4161/pri.6.1.18425|
|Fulltext via DOI:||10.4161/pri.6.1.18425|
|Appare nelle tipologie:||1.1 Journal article|