Conformational Dimorphism and Transmembrane Orientation of Prion Protein Residues 110−136 in Bicelles† Academic Article uri icon

  •  
  • Overview
  •  
  • Research
  •  
  • Identity
  •  
  • Additional Document Info
  •  
  • View All
  •  

abstract

  • A fragment corresponding to the putative membrane-associating domain of the prion protein (residues 110-136) was analyzed in phospholipid bicelles. Prion(110-136) associated with bicelles and exhibited a lipid- and pH-dependent conformational dimorphism between unstructured (pH 4.5) and alpha-helical (pH 7.5). Mutational analysis indicated that the charge state of a single histidine residue was largely responsible for the dimorphism. Amide-lipid NOEs and amide-water chemical exchange measurements revealed that the helical conformation of prion(110-136) spanned the bilayer, and were corroborated by solid-state deuterium NMR experiments indicating that the helical axis rested at a 16 degrees angle with respect to the bilayer normal.

authors

  • Glover, Kerney Jebrell
  • Whiles, Jennifer A
  • Wood, Matthew J
  • Melacini, Giuseppe
  • Komives, Elizabeth A
  • Vold, Regitze R

publication date

  • November 2001