Early onset prion disease from octarepeat expansion correlates with copper binding properties.

ABSTRACT: Insertional mutations leading to expansion of the octarepeat domain of the prion protein (PrP) are directly linked to prion disease. While normal PrP has four PHGGGWGQ octapeptide segments in its flexible N-terminal domain, expanded forms may have up to nine additional octapeptide inserts. The type of prion disease segregates with the degree of expansion. With up to four extra octarepeats, the average onset age is above 60 years, whereas five to nine extra octarepeats results in an average onset age between 30 and 40 years, a difference of almost three decades. In wild-type PrP, the octarepeat domain takes up copper (Cu(2+)) and is considered essential for in vivo function. Work from our lab demonstrates that the copper coordination mode depends on the precise ratio of Cu(2+) to protein. A

SUBMITTER: Stevens DJ 

PROVIDER: S-EPMC2663819 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature