Insight into the conserved structural dynamics of the C-terminus of mammal PrPC identifies structural core and possible structural role of pharmacological chaperones
| Autor: | Patricia Soto, Garrett M. Gloeb, Kaitlin A. Tsuchida, Austin A. Charles, Noah M. Greenwood, Heidi Hendrickson |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Prion, Vol 17, Iss 1, Pp 55-66 (2023) |
| Druh dokumentu: | article |
| ISSN: | 19336896 1933-690X 1933-6896 |
| DOI: | 10.1080/19336896.2023.2186674 |
| Popis: | ABSTRACTMisfolding of the prion protein is central to prion disease aetiology. Although understanding the dynamics of the native fold helps to decipher the conformational conversion mechanism, a complete depiction of distal but coupled prion protein sites common across species is lacking. To fill this gap, we used normal mode analysis and network analysis to examine a collection of prion protein structures deposited on the protein data bank. Our study identified a core of conserved residues that sustains the connectivity across the C-terminus of the prion protein. We propose how a well-characterized pharmacological chaperone may stabilize the fold. Also, we provide insight into the effect on the native fold of initial misfolding pathways identified by others using kinetics studies. |
| Databáze: | Directory of Open Access Journals |
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