ArticlePLoS computational biology2013
Two misfolding routes for the prion protein around pH 4.5.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 18 citations in OpenAlex.
- Prion protein with a mutant N-terminal octarepeat region undergoes cobalamin-dependent assembly into high-molecular weight complexes.The Journal of biological chemistry · 2022Article
- Destabilization of polar interactions in the prion protein triggers misfolding and oligomerization.Protein science : a publication of the Protein Society · 2021Article
- Polymorphism at 129 dictates metastable conformations of the human prion protein N-terminal β-sheet.Chemical science · 2017Article
- The role of Cys179-Cys214 disulfide bond in the stability and folding of prion protein: insights from molecular dynamics simulations.Journal of molecular modeling · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
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Abstract
Using molecular dynamics simulations, we show that the prion protein (PrP) exhibits a dual behavior, with two possible transition routes, upon protonation of H187 around pH 4.5, which mimics specific conditions encountered in endosomes. Our results suggest a picture in which the protonated imidazole ring of H187 experiences an electrostatic repulsion with the nearby guanidinium group of R136, to which the system responds by pushing either H187 or R136 sidechains away from their native cavities. The regions to which H187 and R136 are linked, namely the C-terminal part of H2 and the loop connecting S1 to H1, respectively, are affected in a different manner depending on which pathway is taken. Specific in vivo or in vitro conditions, such as the presence of molecular chaperones or a particular experimental setup, may favor one transition pathway over the other, which can result in very different [Formula: see text] monomers. This has some possible connections with the observation of various fibril morphologies and the outcome of prion strains. In addition, the finding that the interaction of H187 with R136 is a weak point in mammalian PrP is supported by the absence of the [Formula: see text] residue pair in non-mammalian species that are known to be resistant to prion diseases.
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