Structural requirements for efficient prion protein conversion

Gill, Andrew, Agarwal, Sonya, Pinheiro, Teresa J.T. and Graham, James F. (2010) Structural requirements for efficient prion protein conversion. Prion, 4 (4). pp. 235-243. ISSN 1933-6896

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To understand why cross species infection of prion disease often results in inefficient transmission and reduced protein conversion, most research has focussed on defining the effect of variations in PrP primary structures, including sequence compatibility of substrate and seed. By contrast, little research has been aimed at investigating structural differences between different variants of PrPC and secondary structural requirements for efficient conversion. This is despite a clear role for molecular chaperones in formation of prions in non-mammalian systems, indicating the importance of secondary/tertiary structure during the conversion process. Recent data from our laboratory on the cellular location of disease-specific prion cofactors supports the critical role of specific secondary structural motifs and the stability of these motifs in determining the efficiency of disease-specific prion protein conversion. In this paper we summarise our recent results and build on the hypothesis previously suggested by Wuthrich and colleagues, that stability of certain regions of the prion protein is crucial for protein conversion to abnormal isoforms in vivo. It is suggested that one role for molecular co-factors in the conversion process is to stabilise PrPC structure in a form that is amenable for conversion to PrPSc.

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Keywords:prion, Protein Structure, Secondary, protein misfolding, transmissible spongiform encephalopathies
Subjects:C Biological Sciences > C770 Biophysical Science
C Biological Sciences > C760 Biomolecular Science
Divisions:College of Science
ID Code:29481
Deposited On:25 Oct 2018 14:13

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