NR AOUD
AU Hosszu,L.L.P.; Jackson,G.S.; Trevitt,C.R.; Jones,S.; Batchelor,M.; Prodromidou,K.; Clarke,A.R.; Waltho,J.P.; Collinge,J.
TI The residue 129 polymorphism in human prion protein does not confer susceptibility to CJD by altering the structure or stability of PrPc
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-76 and BR-110
PT Konferenz-Poster
AB There are two common isoforms of prion protein (PrP) in humans, with either Methionine or Valine encoded at position 129. This polymorphism is a key determinant of the genetic susceptibility of humans towards both sporadic and acquired forms of prion disease, and to the generation of particular prion disease strains. Despite this, information on the effect of this fundamental mutation on the structure, stability, folding and dynamics of the cellular form of PrP (PrPc) is lacking. Here, we show that the mutation has a barely perceptible effect on the folding, dynamics and stability of PrPc. Apart from relatively minor differences in flexible regions, the tertiary structure of both forms of the protein appear identical. These data indicate that the 129M/V polymorphism does not affect prion disease through PrPc structure and stability, and its effect is likely to be downstream in the disease process; either affecting the stability of other PrP species or the kinetics of their formation.
AD Laszlo L.P. Hosszu, Graham S. Jackson, Clare R. Trevitt, Samantha Jones, Mark Batchelor, Kanella Prodromidou, Anthony R. Clarke, John Collinge, MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, UK; Laszlo L.P. Hosszu, Jonathan P. Waltho, Krebs Institute for Biomolecular Research, Dept. of Molecular Biology and Biotechnology, University of Sheffield, UK
SP englisch
PO Deutschland