Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formation.
The human prion protein (PrP) has a common polymorphism at residue 129, which can be valine or methionine. This polymorphism has a strong influence on susceptibility to prion diseases and on prion-strain properties. Previous work has shown that this amino acid variation has no measurable effect on the native structure of cellular PrP (PrPC). Here, it is shown that the polymorphism does not change the efficiency of conversion to the beta-PrP conformation or affect the binding of copper(II) ions. However, in a partially denatured conformation, the polymorphic variation has a profound influence on the ability of the protein to form amyloid fibrils spontaneously.
Lewis
Patrick A
PA
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Tattum
M Howard
MH
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Jones
Samantha
S
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Bhelt
Daljit
D
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Batchelor
Mark
M
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Clarke
Anthony R
AR
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Collinge
John
J
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Jackson
Graham S
GS
MRC Prion Unit, Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
D000682:Amyloid / Q000378:metabolism*; D003062:Codon; D003300:Copper / Q000378:metabolism; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011487:Protein Conformation
D000682:Amyloid; D003062:Codon; D011328:Prions; D003300:Copper