title: NMR solution structure and membrane interaction of the N-terminal sequence (1-30) of the bovine prion protein.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratory, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Biverståhl
authors.forename: August
authors.initials: A
authors.lastname: Andersson
authors.forename: Astrid
authors.initials: A
authors.lastname: Gräslund
authors.forename: Lena
authors.initials: L
authors.lastname: Mäler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D002942:Circular Dichroism; D004058:Diffusion; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008823:Micelles; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D010742:Phospholipid Ethers / Q000737:chemistry; D011328:Prions / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons; D012694:Serine / Q000737:chemistry; D012996:Solutions / Q000737:chemistry*
chemical_list: C052298:1,2-dihexadecyl-sn-glycero-3-phosphocholine; D008565:Membrane Proteins; D008823:Micelles; D010455:Peptides; D010742:Phospholipid Ethers; D011328:Prions; D011522:Protons; D012996:Solutions; D012694:Serine; D004134:Dimyristoylphosphatidylcholine