The number of octapeptide repeat affects the expression and conversion of prion protein.

The human prion protein (PrP) has five copies of an octapeptide repeat (OR). The mutant PrP with 6-14 OR causes the genetic form of Creutzfeldt-Jakob disease (CJD). To determine the influence of OR on the conversion of PrP, we examined the conversion efficiency of mouse mutant PrP molecules with 1-16 OR in scrapie-infected cells. The expression level of mutant PrP and the glycoform ratio of the abnormal isoform of PrP (PrP(Sc)) were affected by the number of OR. The conversion efficiency was almost equivalent among mutant PrP molecules with 5-16 OR, whereas that of mutant PrP with 1-4 OR was decreased. The present study suggests that CJD patients with the longer extra OR, who usually show only a trace of PrP(Sc) in the brain, can produce the authentic triplet PrP(Sc) if secondary prion infection occurs.