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Early Stages of RNA-Mediated Conversion of Human Prions.

ABSTRACT: Prion diseases are characterized by the conversion of prion proteins from a PrP^C fold into a disease-causing PrP^SC form that is self-replicating. A possible agent to trigger this conversion is polyadenosine RNA, but both mechanism and pathways of the conversion are poorly understood. Using coarse-grained molecular dynamic simulations we study the time evolution of PrP^C over 600 μs. We find that both the D178N mutation and interacting with polyadenosine RNA reduce the helicity of the protein and encourage formation of segments with strand-like motifs. We conjecture that these transient β-strands nucleate the conversion of the protein to the scrapie conformation PrP^SC.

SUBMITTER: Lubecka EA

PROVIDER: S-EPMC9420815 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Early Stages of RNA-Mediated Conversion of Human Prions.

Lubecka Emilia A EA Hansmann Ulrich H E UHE

The journal of physical chemistry. B 20220816 33

Prion diseases are characterized by the conversion of prion proteins from a PrPC fold into a disease-causing PrPSC form that is self-replicating. A possible agent to trigger this conversion is polyadenosine RNA, but both mechanism and pathways of the conversion are poorly understood. Using coarse-grained molecular dynamic simulations we study the time evolution of PrPC over 600 μs. We find that both the D178N mutation and interacting with pol ...[more]

PMID: 35973105

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