@article {370, title = {Solid-state NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {98}, year = {2001}, note = {P Natl Acad Sci USA476PCTimes Cited:51Cited References Count:26}, month = {Sep 25}, pages = {11686-11690}, abstract = {

The secondary structure of a 55-residue fragment of the mouse prion protein, MoPrP(89-143), was studied in randomly aggregated (dried from water) and fibrillar (precipitated from water/ acetonitrile) forms by C-13 solid-state NMR. Recent studies have shown that the fibrillar form of the P101L mutant of MoPrP(89-143) is capable of inducing prion disease in transgenic mice, whereas unaggregated or randomly aggregated samples do not provoke disease. Through analysis of C-13 chemical shifts, we have determined that both wild-type and mutant sequence MoPrP(89-143) form a mixture of beta -sheet and alpha -helical conformations in the randomly aggregated state although the beta -sheet content in MoPrP(89-143, P101L) is significantly higher than in the wild-type peptide. In a fibrillar state, MoPrP(89-143, P101L) is completely converted into beta -sheet, suggesting that the formation of a specific beta -sheet structure may be required for the peptide to induce disease. Studies of an analogous peptide from Syrian hamster PrP verify that sequence alterations in residues 101-117 affect the conformation of aggregated forms of the peptides.

}, keywords = {diseases}, isbn = {0027-8424}, doi = {Doi 10.1073/Pnas.201404298}, url = {://WOS:000171237100125}, author = {Laws, D. D. and Bitter, H. M. L. and Liu, K. and Ball, H. L. and Kaneko, K. and Wille, H. and Cohen, F. E. and Prusiner, S. B. and Pines, A. and Wemmer, D. E.} }