Effect of enzymatic deimination on the conformation of recombinant prion protein

• Published in: Biochimica et biophysica acta 2009-08, Vol.1794 (8), p.1123-1133
• Main Authors: Young, Duncan S., Meersman, Filip, Oxley, David, Webster, Judith, Gill, Andrew C., Bronstein, Igor, Lowe, Christopher R., Dear, Denise V.
• Format: Article
• Language: English
• Subjects: Amyloid; Anilino Naphthalenesulfonates; Animals; Arginine - chemistry; Arginine - metabolism; Arginine modification; Birefringence; Circular Dichroism; Citrulline; Citrulline - chemistry; Citrulline - metabolism; Conformational change; Deimination; Electrophoresis, Polyacrylamide Gel; Endopeptidase K - metabolism; Fluorescent Dyes; Post-translational modification; Prion protein; Prions - chemistry; Protein Conformation - drug effects; Protein Processing, Post-Translational; Recombinant Proteins - chemistry; Sheep; Spectroscopy, Fourier Transform Infrared
• ISSN: 1570-9639; 0006-3002; 1878-1454
• DOI: 10.1016/j.bbapap.2009.03.013

Deimination is the post-translational conversion of arginine residues to citrulline. It has been implicated as a causative factor in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis and more recently, as a marker of neurodegeneration. We have investigated the effect of the post-translational modification of arginine residues on the structure of recombinant ovine prion protein. Deiminated prion protein exhibited biophysical properties characteristic of the scrapie-associated conformer of prion protein viz. an increased β-sheet secondary structure, congophilic structures indicative of amyloid and proteinase K resistance which could be templated onto normal unmodified prion protein. In the light of these findings, a potential role of post-translational modifications to prion protein in disease initiation or propagation is discussed.