NR AQHV
AU Biro,J.C.
TI The prion paradox: infection or polymerisation?
QU Applied Bioinformatics 2003; 2(3 Suppl): S25-30
PT journal article
AB A weak but significant similarity was found between the prion protein (PrP) and some transcription factors and zinc-finger proteins. A possible interpretation of this similarity is that the PrP is a metal- (copper-) binding transcription factor and might behave like a Zn-finger protein, with the Cu2+ binding to its histidine and serine residues. Copper-binding could create intramolecular bridges in the PrPc (normal, cytoplasmic) molecule, but intermolecular bridges in the PrPsc (scrapie pathogenic) molecule. A molecular model of the Cu2+ -binding monomeric PrPc and the Cu2+-stabilised polymeric PrPsc is presented here and named the 'cuprion model'. In this model, the PrPc has two idioforms. The stable, normal PrPc-idioform-I contains Cu2+ in -2His-Cu2+-2His- complexes and an intramolecular disulphide bridge. An unstable, transient form, PrPc-idioform-II, contains a -2His-Cu 2+-2Cys- complex, which destabilises the intramolecular disulphide bridge and makes the PrPc molecule highly reactive with other PrPc molecules.
MH Amino Acid Sequence; Animals; Binding Sites; Central Nervous System Infections/metabolism; Dimerization; Human; *Models, Biological; Models, Chemical; *Models, Molecular; Molecular Sequence Data; PrPc Proteins/chemistry/metabolism; PrPsc Proteins/chemistry/metabolism; Prion Diseases/metabolism; Prions/*chemistry/*metabolism; Protein Binding; Protein Conformation; *Sequence Homology, Amino Acid; Structure-Activity Relationship; Transcription Factors/chemistry/metabolism
AD Homulus Informatics, San Francisco, CA 94105, USA. jan.brio@kbh.ki.se
SP englisch
PO Neuseeland