Insight into the conserved structural dynamics of the C-terminus of mammal PrPC identifies structural core and possible structural role of pharmacological chaperones.

Autor:	Soto P; Physics department, Creighton University, Omaha, NE, USA., Gloeb GM; Chemistry department, Creighton University, Omaha, NE, USA., Tsuchida KA; Physics department, Creighton University, Omaha, NE, USA., Charles AA; Chemistry department, Creighton University, Omaha, NE, USA., Greenwood NM; Physics department, Creighton University, Omaha, NE, USA., Hendrickson H; Chemistry department, Lafayette College, Easton, PA, USA.
Jazyk:	angličtina
Zdroj:	Prion [Prion] 2023 Dec; Vol. 17 (1), pp. 55-66.
DOI:	10.1080/19336896.2023.2186674
Abstrakt:	Misfolding 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:	MEDLINE
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