mechanistic prospective for human prpc conversion to prpsc: molecular dynamic insights

نویسندگان

nooshin azari

mohammad reza dayer

nematollah razmi

mohammad saaid dayer

چکیده

prpc conversion to prpsc isoform is the main known cause for prion diseases including crutzfeldt-jakob, gerstmann-sträussler-sheinker syndrome and fatal familial insomnia in human. the precise mechanism underling this conversion is yet to be well understood. in the present work,  using the coordinate file of prpc (available on the protein data bank) as a starting structure, separate molecular dynamic simulations were carried out at neutral and acidic ph in an explicit water box at 37°c and 1 atmosphere pressure for 10ns second period. results showed that the acidic ph accelerates prpc conversion to prpsc by decreasing the protein gyration radius, flexibility and protein-solvent hydrogen bonds. in acidic conditions, prpc attains a more folded and less flexible tertiary structure compared to its native structure at neutral ph; otherwise, the decrease of protein-solvent hydrogen bonds at acidic ph will enhance the hydrophobic character of prpc that may exhibit association as multimeric assemblies. it can also lower water solubility and increase resistance to proteolytic degradations. data indicated that there was no sensible protein denaturation during this conversion. it is hypothesized that the formation of slightly misfolded conformations with minor structural changes in secondary and/or tertiary structures are enough to menace scrapie formation in prpc. our findings show that scrapie formation seems to be a theoretically reversible process.

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Mechanistic prospective for human PrPC conversion to PrPSc: Molecular dynamic insights

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عنوان ژورنال:
molecular biology research communications

ناشر: shiraz university press

ISSN 2322-181X

دوره 2

شماره 4 2013

میزبانی شده توسط پلتفرم ابری doprax.com

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