Human prion protein

Jackson, G. S. et al. Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations. Science 283 1935-1937,1999. 

Asante, E. A. et al. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J. 21 6358-6366,2002. 

NMR characterization of the recombinant mouse,hamster, bovine and human prion proteins showed that all these molecules share a common architecture, consisting of a flexible unstructured N-terminal tail of about 100 residues from position 23 to position 124 attached to a globular domain within residues 125-228. The globular domain contains a double-stranded anti-parallel /1-sheet and three ot-helices (Fig. 6). 

Monoclonal antibodies 3F4 (Senetk, St. Louis, MO) and F89/160.1.5 are used for immunostaining of prion protein. The monoclonal antibody 3F4 was developed by Kascsack et al. (1987) and shows immunoreactivity with the epitope around AA 112 of the human prion protein. The monoclonal antibody F89/160.1.5 was developed at the U.S. Department of Agriculture against a synthetic peptide representing residues 146-159 of... 

The antimalarial drug quinacrine and some phenothiazine derivatives, acepro-mazine, chlorpromazine, and promazine, have been used for the treatment of prion diseases (Doh-ura et al., 2000 Korth et al., 2001 May et al., 2003). The molecular mechanism associated with the inhibition of PrPsc formation by quinacrine remains unknown. However, it is proposed that quinacrine binds with human prion protein at the Tyr-225, Tyr-226, and Gln-227 residues of helix 3 (Vogtherr et al., 2003) and provides neuroprotection. Quinacrine may also act as an antioxidant and reduce the toxicity of prP 6 (Turnbull et al., 2003). 

Makiinou E, Collinge J, Antoniou M (2002) Genomic chai acterizadon of die human prion protein (PrP) gene locus. Mamm Genome 13 696-703. 

Gerstmann-Straussler-Sclieinker (GSS) syndrome is a prion disease linked to germ line mutations or insertions in the human prion protein gene resulting in a neurodegenerative brain disorder. 

Zahn R, Liu A, Luhrs T et al (2000) NMR solution structure of the human prion protein. Proc Natl Acad Sci USA 97 145-150... 

Fig. 1 Diagram of the human prion protein gene showing the octapeptide repeat region (51-91), regions of predicted secondary structure [designated a (helical) or [3 (sheet)], pathogenic or likely pathogenic mutations (above in red), non-synonymous polymorphisms and synonymous polymorphisms (below in green)...

Baker HE, Poulter M, Crow TJ et al (1991) Aminoacid polymorphism in human prion protein and age at death in inherited prion disease. Lancet 337 1286... 

Sandberg MK, Al Doujaily H, Sigurdson CJ et al (2010) Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein. J Gen Virol 91 2651-2657... 

Wadsworth JD, Asante EA, Desbruslais M, Linehan JM, Joiner S, Gowland I, Welch J, Stone L, Lloyd SE, Hill AF, Brandner S, Collinge J (2004) Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science 306 1793-1796... 

Beringue V, Herzog L, Reine F, Le Dur A, Casalone C, Vilotte JL, Laude H (2008) Transmission of atypical bovine prions to mice transgenic for human prion protein. Emerg Infect Dis 14 1898-1901... 

Collinge J, Palmer MS, Sidle KC, Hill AF, Gowland I, Meads J, Asante E, Bradley R, Doey LJ, Lantos PL (1995) Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature 378 779-783... 

Zhang Y, Swietnicki W, Zagorski MG et al (2000) Solution structure of the E200K variant of human prion protein. Implications for the mechanism of pathogenesis in familial prion... 

Knaus KJ, Morillas M, Swietnicki W et al (2001) Crystal structure of the human prion protein reveals a mechanism for oligomerization. Nat Struct Biol 8 770-774... 

Antonyuk SV, Trevitt CR, Strange RW et al (2009) Crystal structure of human prion protein bound to a therapeutic antibody. Proc Natl Acad Sci USA 106 2554-2558... 

Calzolai L, Zahn R (2003) Influence of pH on NMR structure and stability of the human prion protein globular domain. J Biol Chem 278 35592-35596... 

Hosszu LLP, Tattum MH, tones S et al (2010) The H187R mutation of the human prion protein induces conversion of recombinant prion protein to the PrP(Sc)-like form. Biochemistry 49 8729-8738... 

Hosszu LLP, Wells MA, Jackson GS et al (2005) Definable equilibrium states in the folding of human prion protein. Biochemistry 44 16649-16657... 

Apetri AC, Surewicz K, Surewicz WK (2004) The effect of disease-associated mutations on the folding pathway of human prion protein. J Biol Chem 279 18008-18014... 

Apetri AC, Maki K, Roder H et al (2006) Early intermediate in human prion protein folding as evidenced by ultrarapid mixing experiments. J Am Chem Soc 128 11673-11678... 

Hart T, Hosszu LLP, Trevitt CR et al (2009) Folding kinetics of the human prion protein probed by temperature jump. Proc Natl Acad Sci USA 106 5651-5656... 

Swietnicki W, Petersen RB, Gambetti P et al (1998) Familial mutations and the thermodynamic stability of the recombinant human prion protein. J Biol Chem 273 31048-31052... 

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