Structural features of prions explored by sequence analysis. II. A PrP(Sc) model.
Prion diseases are neurodegenerative disorders associated with a conformational conversion of the prion PrP protein, in which the beta strand content increases and that of the a helix decreases. However, the structure of the pathogenous form PrP(Sc), occurring after conformational conversion of the normal cellular form PrP(C), is not yet known. From sequence analysis, we have previously proposed that helix H2 of the prion PrP(C) structure might be a key region for this structural conversion. More recently, we identified the TATA box-binding protein fold as a putative scaffold that may locally satisfy the predicted secondary-structure organisation of PrP(Sc). In the present analysis, we detail the schematic construction of PrP(Sc) monomeric and dimeric models, based on this hypothesis. These models are globally compatible with available data and therefore may provide further insights into the structurally and functionally elusive PrP protein. Some comments are also devoted to a comparison of the yeast Ure2p prion and animal prions.
Mornon
J P
JP
Systèmes Moléculaires & Biologie Structurale, LMCP, CNRS UMR 7590, Universités Paris 6 et Paris 7, case 115, 4 place Jussieu, 75252 Paris Cedex 05, France. mornon@lmcp.jussieu.fr
Prat
K
K
Dupuis
F
F
Boisset
N
N
Callebaut
I
I
D000595:Amino Acid Sequence; D000818:Animals; D019281:Dimerization; D005979:Glutathione Peroxidase; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018620:PrPSc Proteins / Q000737:chemistry* / Q000378:metabolism; D011328:Prions / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D020539:Sequence Analysis, Protein
D018620:PrPSc Proteins; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae