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• W3023290949 abstract "The conserved central region (CR) of PrPC has been hypothesized to serve as a passive linker connecting the protein's toxic N-terminal and globular C-terminal domains. Yet, deletion of the CR causes neonatal fatality in mice, implying the CR possesses a protective function. The CR encompasses the regulatory α-cleavage locus, and additionally facilitates a regulatory metal ion-promoted interaction between the PrPC N- and C-terminal domains. To elucidate the role of the CR and determine why CR deletion generates toxicity, we designed PrPC constructs wherein either the cis-interaction or α-cleavage are selectively prevented. These constructs were interrogated using nuclear magnetic resonance, electrophysiology, and cell viability assays. Our results demonstrate the CR is not a passive linker and the native sequence is crucial for its protective role over the toxic N-terminus, irrespective of α-cleavage or the cis-interaction. Additionally, we find that the CR facilitates homodimerization of PrPC, attenuating the toxicity of the N-terminus." @default.
• W3023290949 created "2020-05-13" @default.
• W3023290949 creator A5004816906 @default.
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• W3023290949 creator A5075994602 @default.
• W3023290949 creator A5084855980 @default.
• W3023290949 date "2020-05-08" @default.
• W3023290949 modified "2023-10-14" @default.
• W3023290949 title "Intrinsic toxicity of the cellular prion protein is regulated by its conserved central region" @default.
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• W3023290949 doi "https://doi.org/10.1096/fj.201902749rr" @default.
• W3023290949 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7442283" @default.
• W3023290949 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32385908" @default.
• W3023290949 hasPublicationYear "2020" @default.
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