A model for prion protein dimerisation based on alpha-helical packing.
Residues 109-122 of the human prion protein (PrP) are highly conserved across species, and are predicted to be alpha-helical in PrPc, the cellular form. A computational search of the potential for alpha-helical dimerisation has been made for residues 109-122. The conformation which consistently scores highest in terms of burying non-polar surface area is a tight association involving alanine, glycine and valine residues. A model of heterodimerisation for PrPc and PrPSc (the misfolded form) is presented in which species barrier mutations would arise from interaction specificities that would follow, at least in part, the same framework as formation of a putative homodimer.
Warwicker
J
J
Institute of Food Research, Reading Laboratory, United Kingdom. james.warwicker@bbsrc.ac.uk
Gane
P J
PJ
D000409:Alanine; D000595:Amino Acid Sequence; D003198:Computer Simulation; D019281:Dimerization; D005998:Glycine; D006801:Humans; D008958:Models, Molecular; D008961:Models, Structural; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011328:Prions / Q000737:chemistry*; D021382:Protein Sorting Signals / Q000737:chemistry; D017433:Protein Structure, Secondary; D014633:Valine
D010446:Peptide Fragments; D011328:Prions; D021382:Protein Sorting Signals; D014633:Valine; D000409:Alanine; D005998:Glycine