An unusual soluble beta-turn-rich conformation of prion is involved in fibril formation and toxic to neuronal cells
UNSPECIFIED. (2005) An unusual soluble beta-turn-rich conformation of prion is involved in fibril formation and toxic to neuronal cells. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 328 (1). pp. 292-305. ISSN 0006-291XFull text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.bbrc.2004.12.172
A key molecular event in prion diseases is the conversion of the prion protein (PrP) from its normal cellular form (PrPC) to the disease-specific form (PrPSc). The transition from PrPC to PrPSc involves a major conformational change, resulting in amorphous protein aggregates and fibrillar amyloid deposits with increased beta-sheet structure. Using recombinant PrP refolded into a beta-sheet-rich form (beta-PrP) we have studied the fibrillization of beta-PrP both in solution and in association with raft membranes. In low ionic strength thick dense fibrils form large networks, which coexist with amorphous aggregates. High ionic strength results in less compact fibrils, that assemble in large sheets packed with globular PrP particles, resembling diffuse aggregates found in ex vivo preparations of PrPSc. Here we report on the finding of a beta-turn-rich conformation involved in prion fibrillization that is toxic to neuronal cells in culture. This is the first account of an intermediate in prion fibril formation that is toxic to neuronal cells. We propose that this unusual beta-turn-rich form of PrP may be a precursor of PrPSc and a candidate for the neurotoxic molecule in prion pathogenesis. (C) 2005 Elsevier Inc. All rights reserved.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
|Journal or Publication Title:||BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS|
|Publisher:||ACADEMIC PRESS INC ELSEVIER SCIENCE|
|Date:||4 March 2005|
|Number of Pages:||14|
|Page Range:||pp. 292-305|
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