Most of the structural elements of the globular domain of murine prion protein form fibrils with predominant beta-sheet structure.
The conversion of the cellular prion protein into the beta-sheet-rich scrapie prion protein is thought to be the key step in the pathogenesis of prion diseases. To gain insight into this structural conversion, we analyzed the intrinsic structural propensity of the amino acid sequence of the murine prion C-terminal domain. For that purpose, this globular domain was dissected into its secondary structural elements and the structural propensity of the protein fragments was determined. Our results show that all these fragments, excepted that strictly encompassing helix 1, have a very high propensity to form structured aggregates with a dominant content of beta-sheet structures.
Jamin
Nadège
N
CEA-Saclay, DBJC and URA CNRS 2096, Bât. 532, 91191 Gif sur Yvette Cedex, France. jamin@dsvidf.cea.fr
Coïc
Yves-Marie
YM
Landon
Céline
C
Ovtracht
Ludmila
L
Baleux
Françoise
F
Neumann
Jean-Michel
JM
Sanson
Alain
A
D000595:Amino Acid Sequence; D000818:Animals; D051379:Mice; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011328:Prions / Q000737:chemistry* / Q000648:ultrastructure; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared
D011328:Prions