H. Wille et Sb. Prusiner, Ultrastructural studies on scrapie prion protein crystals obtained from reverse micellar solutions, BIOPHYS J, 76(2), 1999, pp. 1048-1062
The structural transition from the cellular prion protein (PrPC) that is ri
ch in alpha-helices to the pathological form (PrPSc) that has a high beta-s
heet content seems to be the fundamental event underlying the prion disease
s. Determination of the structure of PrPSc and the N-terminally truncated P
rP 27-30 has been complicated by their insolubility. Here we report the sol
ubilization of PrP 27-30 through a system of reverse micelles that yields m
onomeric and dimeric PrP. Although solubilization of PrP 27-30 was not acco
mpanied by any recognizable change in secondary structure as measured by FT
IR spectroscopy, it did result in a loss of prion infectivity. The formatio
n of small two- and three-dimensional crystals upon exposure to uranyl salt
s argues that soluble PrP 27-30 possesses considerable tertiary structure.
The crystals of PrP 27-30 grown from reverse micellar solutions suggest a n
ovel crystallization mechanism that might be applicable for other membrane
proteins. A variety of different crystal lattices diffracted up to 1.85 nm
by electron microscopy. Despite the lack of measurable biological activity,
the structure of PrP 27-30 in these crystals may provide insight into the
structural transition that occurs during PrP(Sc)formation.