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

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.

Title	Insight into the conserved structural dynamics of the C-terminus of mammal PrPC identifies structural core and possible structural role of pharmacological chaperones
Creator	Hendrickson, Heidi P.
	Gloeb, G. M.
	Soto, P.
	Charles, A. A.
	Greenwood, N. M.
	Tsuchida, K. A.
Publisher	Prion
Academic Department	Chemistry
Division	Natural Sciences
Organization	Lafayette College
Date Issued	2023
Date Available	2023-03-14
Type	Article
Language	English
Keyword	normal mode analysis
	Collective motions
	network analysis
	Prion protein
	structural dynamics
Bibliographic Citation	Soto, P., et al. (2023) "Insight into the conserved structural dynamics of the C-terminus of mammal PrPC identifies structural core and possible structural role of pharmacological chaperones." Prion 17 (1): 55-66.
Standard Identifier	Handle 10385/5138jg280
Standard Identifier	DOI 10.1080/19336896.2023.2186674
Permalink	http://hdl.handle.net/10385/5138jg280
Rights Statement	Creative Commons - Attribution, Non-Commercial
Rights Holders	Creighton University