Structural requirements for efficient prion protein conversion : cofactors may promote a conversion-competent structure for PrPC
Gill, Andrew C., Agarwal, Sonya, Pinheiro, Teresa J. T. and Graham, James F.. (2010) Structural requirements for efficient prion protein conversion : cofactors may promote a conversion-competent structure for PrPC. Prion, Vol.4 (No.4). pp. 235-243. ISSN 1933-6896Full text not available from this repository.
Official URL: http://dx.doi.org/10.4161/pri.4.4.13394
To understand why cross-species infection of prion disease often results in inefficient transmission and reduced protein conversion, most research has focused 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 PrP(C) 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 summarize 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 cofactors in the conversion process is to stabilize PrP(C) structure in a form that is amenable for conversion to PrP(Sc).
|Item Type:||Journal Article|
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Divisions:||Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)|
|Journal or Publication Title:||Prion|
|Page Range:||pp. 235-243|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Biotechnology and Biological Sciences Research Council (BBSRC)|
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