Prion protein: Difference between revisions
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==Prion strains== | ==Prion strains== | ||
The phenomenon of prion strains (disease subtypes with specific clinical, biochemical and neuropathological features, replicating with high fidelity) was initially difficult to equate with the "protein only" hypothesis of prion diseases. However, there is now evidence from a range if studies suggesting that strains are enciphered in the structure of PrP<sup>Sc</sup>. One potential mechanism for this is alternate threading of the β-helix. | The phenomenon of prion strains (disease subtypes with specific clinical, biochemical and neuropathological features, replicating with high fidelity) was initially difficult to equate with the "protein only" hypothesis of prion diseases. However, there is now evidence from a range if studies suggesting that strains are enciphered in the structure of PrP<sup>Sc</sup>. One potential mechanism for this is alternate threading of the β-helix. | ||
==Hot Spots in PrP<sup>C</sup> for pathogenic conversion== | |||
There are several point mutations associated with known human prion diseases (P102L, P105L, A117V, M129V, G131V, Y145Stop, R148H, Q160Stop, D178N, V180I, T183A, H187R, T188R, E196K, F198S, E200K, D202N, V203I, R208H, V210I, E211Q, Q212P, and Q217R). | |||
The pathogenic conversion process from PrP<sup>C</sup> to PrP<sup>Sc</sup> could be related to the thermal stability of PrP<sup>C</sup> <ref>Kuwata, K. ''et al.'' (2007) Hot spots in prion protein for pathogenic conversion ''Proc. Natl. Acad. Sci. USA'' '''104''', 11921–11926</ref>, since the mutations related to familial forms of the prion diseases are rather concentrated in helices 2 and 3, and the thermodynamical stability profile shows that diverse residues in helices 2 and 3 are less stable <ref>Kuwata, K. ''et al.'' (2002) Locally disordered conformer of the hamster prion protein: a crucial intermediate to PrP<sup>Sc</sup> ''Biochemistry '' '''41''', 12277–12283</ref>. | |||
Moreover, the conversion might also be related with the global conformational fluctuation of PrP<sup>C</sup>, as a Carr–Purcell–Meiboom–Gill relaxation–dispersion | |||
study revealed that slow fluctuation on a time scale of microseconds to milliseconds occurs, again, in helices 2 and 3<ref>Kuwata, K. ''et al.'' (2004) Slow conformational dynamics in the hamster prion protein ''Biochemistry'' '''43''', 4439-4446</ref>,<ref>Korzhnev, D.M. ''et al.'' (2004) Low-populated folding intermediates of Fyn SH3 characterized by relaxation dispersion NMR ''Nature'' '''430''', 586-590</ref>. | |||
==Selected PrP structures== | ==Selected PrP structures== | ||