NR ARFV
AU Blanch,E.W.; Gill,A.C.; Rhie,A.G.; Hope,J.; Hecht,L.; Nielsen,K.; Barron,L.D.
TI Raman optical activity demonstrates poly(L-proline) II helix in the N-terminal region of the ovine prion protein: implications for function and misfunction.
QU Journal of Molecular Biology 2004 Oct 15; 343(2): 467-76
PT journal article
AB The aqueous solution structure of the full-length recombinant ovine prion protein PrP(25-233), together with that of the N-terminal truncated version PrP(94-233), have been studied using vibrational Raman optical activity (ROA) and ultraviolet circular dichroism (UVCD). A sharp positive band at approximately 1315 cm(-1) characteristic of poly(L-proline) II (PPII) helix that is present in the ROA spectrum of the full-length protein is absent from that of the truncated protein, together with bands characteristic of beta-turns. Although it is not possible similarly to identify PPII helix in the full-length protein directly from its UVCD spectrum, subtraction of the UVCD spectrum of PrP(94-233) from that of PrP(25-233) yields a difference UVCD spectrum also characteristic of PPII structure and very similar to the UVCD spectrum of murine PrP(25-113). These results provide confirmation that a major conformational element in the N-terminal region is PPII helix, but in addition show that the PPII structure is interspersed with beta-turns and that little PPII structure is present in PrP(94-233). A principal component analysis of the ROA data indicates that the alpha-helix and beta-sheet content, located in the structured C-terminal domain, of the full-length and truncated proteins are similar. The flexibility imparted by the high PPII content of the N-terminal domain region may be an essential factor in the function and possibly also the misfunction of prion proteins.
MH Amino Acid Sequence; Animals; Circular Dichroism/methods; Models, Molecular; Molecular Sequence Data; Prions/*chemistry/genetics/metabolism; Proline/*chemistry/metabolism; *Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins/chemistry/genetics/metabolism; Research Support, Non-U.S. Gov't; Sequence Alignment; Sheep; *Spectrum Analysis, Raman
AD Department of Chemistry, University of Glasgow, G12 8QQ, UK
SP englisch
PO England