Structural insights into alternate aggregated prion protein forms.

Authors:
Dr. Alpan Bek, PhD
Dr. Alpan Bek, PhD
Middle East Technical University
Associate Professor
Nano-Optics, plasmonics
Ankara | Turkey

J Mol Biol 2009 Nov 28;393(5):1033-42. Epub 2009 Aug 28.

Laboratory of Prion Biology, Neurobiology Sector, Scuola Internazionale Superiore di Studi Avanzati-International School of Advanced Studies (SISSA-ISAS) Edificio Q1, Area Science Park, SS 14 Km 163.5, I-34149 Basovizza (TS), Italy.

The conversion of the cellular form of the prion protein (PrP(C)) to an abnormal, alternatively folded isoform (PrP(Sc)) is the central event in prion diseases or transmissible spongiform encephalopathies. Recent studies have demonstrated de novo generation of murine prions from recombinant prion protein (recPrP) after inoculation into transgenic and wild-type mice. These so-called synthetic prions lead to novel prion diseases with unique neuropathological and biochemical features. Moreover, the use of recPrP in an amyloid seeding assay can specifically detect and amplify various strains of prions. We employed this assay in our experiments and analyzed in detail the morphology of aggregate structures produced under defined chemical constraints. Our results suggest that changes in the concentration of guanidine hydrochloride can lead to different kinetic traces in a typical thioflavin T(ThT) assay. Morphological and structural analysis of these aggregates by atomic force microscopy indicates a variation in the structure of the PrP molecular assemblies. In particular, ThT positive PrP aggregates produced from rec mouse PrP residues 89 to 230 lead to mostly oligomeric structures at low concentrations of guanidine hydrochloride, while more amyloidal structures were observed at higher concentrations of the denaturant. These findings highlight the presence of numerous and complex pathways in deciphering prion constraints for infectivity and toxicity.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2009.08.056DOI Listing
November 2009
3 Reads
8 Citations
4.333 Impact Factor

Publication Analysis

Top Keywords

prion protein
12
guanidine hydrochloride
8
prion diseases
8
prion
6
chemical constraints
4
lead kinetic
4
kinetic traces
4
hydrochloride lead
4
constraints changes
4
concentration guanidine
4
traces typical
4
changes concentration
4
ttht assay
4
analysis aggregates
4
aggregates atomic
4
atomic force
4
structural analysis
4
morphological structural
4
thioflavin ttht
4
defined chemical
4

Similar Publications