TY  - JOUR
AU  - Redecke, L.
AU  - Binder, S.
AU  - Elmallah, M. I. Y.
AU  - Broadbent, R.
AU  - Tilkorn, C.
AU  - Schulz, B.
AU  - May, P.
AU  - Goos, A.
AU  - Ruebhausen, M.
AU  - Betzel, C.
AU  - DESY
TI  - UV light induced conversion and aggregation of prion proteins.
JO  - Free radical biology and medicine
VL  - 46
SN  - 0891-5849
CY  - New York, NY [u.a.]
PB  - Elsevier
M1  - PHPPUBDB-20359
SP  - 1353-1361
PY  - 2009
N1  - © Elsevier Inc.
AB  - Increasing evidence suggests a central role for oxidative stress in the pathology of prion diseases, a group of fatal neurodegenerative disorders associated with structural conversion of the prion protein (PrP). Because UV-light-induced protein damage is mediated by direct photo-oxidation and radical reactions, we investigated the structural consequences of UVB radiation on recombinant murine and human prion proteins at pH 7.4 and pH 5.0. As revealed by circular dichroism and dynamic light scattering measurements, the observed PrP aggregation follows two independent pathways: (i) complete unfolding of the protein structure associated with rapid precipitation or (ii) specific structural conversion into distinct soluble beta-oligomers. The choice of pathway was directly attributed to the chromophoric properties of the PrP species and the susceptibility to oxidation. Regarding size, the oligomers characterized in this study share a high degree of identity with oligomeric species formed after structural destabilization induced by other triggers, which significantly strengthens the theory that partly unfolded intermediates represent initial precursor molecules directing the pathway of PrP aggregation. Moreover, we identified the first suitable photo-trigger capable of inducing refolding of PrP, which has an important biotechnological impact in terms of analyzing the conversion process on small time scales.
KW  - Animals
KW  - Circular Dichroism
KW  - Humans
KW  - Mice
KW  - Oxidation-Reduction
KW  - PrPC Proteins: chemistry
KW  - PrPC Proteins: radiation effects
KW  - PrPSc Proteins: chemistry
KW  - PrPSc Proteins: radiation effects
KW  - Prion Diseases: etiology
KW  - Prion Diseases: physiopathology
KW  - Protein Conformation
KW  - Protein Folding
KW  - Protein Multimerization
KW  - Protein Processing, Post-Translational
KW  - Recombinant Proteins: chemistry
KW  - Recombinant Proteins: radiation effects
KW  - Solubility
KW  - Ultraviolet Rays
KW  - PrPC Proteins (NLM Chemicals)
KW  - PrPSc Proteins (NLM Chemicals)
KW  - Recombinant Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:19249347
UR  - <Go to ISI:>//WOS:000267322900005
DO  - DOI:10.1016/j.freeradbiomed.2009.02.013
UR  - https://bib-pubdb1.desy.de/record/94625
ER  -