title: Conformational dimorphism and transmembrane orientation of prion protein residues 110-136 in bicelles.
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.affiliation: Department of Chemistry and Biochemistry, 0359, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0359, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Glover
authors.forename: J A
authors.initials: JA
authors.lastname: Whiles
authors.forename: M J
authors.initials: MJ
authors.lastname: Wood
authors.forename: G
authors.initials: G
authors.lastname: Melacini
authors.forename: E A
authors.initials: EA
authors.lastname: Komives
authors.forename: R R
authors.initials: RR
authors.lastname: Vold
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D002942:Circular Dichroism; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D010713:Phosphatidylcholines / Q000737:chemistry; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence
chemical_list: D008051:Lipid Bilayers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D011328:Prions