Conformational dimorphism and transmembrane orientation of prion protein residues 110-136 in bicelles.
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.
Glover
K J
KJ
Department of Chemistry and Biochemistry, 0359, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0359, USA.
Whiles
J A
JA
Wood
M J
MJ
Melacini
G
G
Komives
E A
EA
Vold
R R
RR
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
D008051:Lipid Bilayers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D011328:Prions