1skh

Publication Abstract from PubMed

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.

NMR solution structure and membrane interaction of the N-terminal sequence (1-30) of the bovine prion protein.,Biverstahl H, Andersson A, Graslund A, Maler L Biochemistry. 2004 Nov 30;43(47):14940-7. PMID:15554701^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.