NR ARFU
AU Biverstahl,H.; Andersson,A.; Gräslund,A.; Maler,L.
TI NMR solution structure and membrane interaction of the N-terminal sequence (1-30) of the bovine prion protein
QU Biochemistry 2004 Nov 30; 43(47): 14940-7
PT journal article
AB The structure and membrane interaction of the N-terminal sequence (1-30) of the bovine prion protein (bPrPp) has been investigated by NMR spectroscopy in phospholipid membrane mimetic systems. CD spectroscopy revealed that the peptide adopts a largely alpha-helical structure in zwitterionic bicelles as well as in DHPC micelles but has a less degree of alpha-helix structure in partly charged bicelles. The solution structure of bPrPp was determined in DHPC micelles, and an alpha-helix was found between residues Ser8 and Ile21. The residues within the helical region show slow amide hydrogen exchange. Translational diffusion measurements in zwitterionic q = 0.5 bicelles show that the peptide does not induce aggregation of the bicelles. Increased quadrupolar splittings were observed in the outer part of the (2)H spectrum of DMPC in q = 3.5 bicelles, indicating that the peptide induces a certain degree of order in the bilayer. The amide hydrogen exchange and the (2)H NMR results are consistent with a slight positive hydrophobic mismatch and that bPrPp forms a stable helix that inserts in a transmembrane location in the bilayer. The structure of bPrPp and its position in the membrane may be relevant for the understanding of how the N-terminal (1-30) part of the bovine PrP functions as a cell-penetrating peptide. These findings may lead to a better understanding of how the prion protein accumulates at the membrane surface and also how the conversion into the scrapie form is carried out.
MH Amino Acid Sequence; Animals; Cattle; Cell Membrane/*metabolism; Circular Dichroism; Diffusion; Dimyristoylphosphatidylcholine/chemistry; Hydrophobicity; Membrane Proteins/chemistry/*metabolism; Micelles; Models, Molecular; *Nuclear Magnetic Resonance, Biomolecular; Peptides/*chemistry; Phospholipid Ethers/chemistry; Prions/*chemistry; Protein Structure, Secondary; Protein Structure, Tertiary; Protons; Research Support, Non-U.S. Gov't; Serine/chemistry; Solutions/*chemistry
AD Department of Biochemistry and Biophysics, Arrhenius Laboratory, Stockholm University, 10691 Stockholm, Sweden.
SP englisch
PO USA