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. and Gill, Andrew and Rhie, Alexandre G.O. and Hope, James and Hecht, Lutz and 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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