Raman Optical Activity Demonstrates Poly(l-proline) II Helix in the N-terminal Region of the Ovine Prion Protein: Implications for Function and Misfunction

Blanch, Ewan W., Gill, Andrew, Rhie, Alexandre G.O., Hope, James, Hecht, Lutz, Nielsen, Kurt and Barron, Laurence D. (2004) Raman Optical Activity Demonstrates Poly(l-proline) II Helix in the N-terminal Region of the Ovine Prion Protein: Implications for Function and Misfunction. Journal of Molecular Biology, 343 (2). pp. 467-476. ISSN 0022-2836

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Abstract

The aqueous solution structure of the full-length recombinant ovine prion protein PrP25-233, together with that of the N-terminal truncated version PrP94-233, have been studied using vibrational Raman optical activity (ROA) and ultraviolet circular dichroism (UVCD). A sharp positive band at similar to1315 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 PrP94-233 from that of PrP25-233 yields a difference UVCD spectrum also characteristic of PPII structure and very similar to the UVCD spectrum of murine PrP25-113. 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 PrP94-233. 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.

Keywords:prion protein, transmissible spongiform encephalopathies, polyproline helix, raman optical activity, amyloid fibrils
Subjects:C Biological Sciences > C760 Biomolecular Science
Divisions:College of Science
ID Code:29569
Deposited On:30 Aug 2018 10:06

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