gc; PRION
gx; PR00341
gt; Prion protein signature
gp; INTERPRO; IPR000817
gp; PROSITE; PS00291 PRION_1; PS00706 PRION_2
gp; BLOCKS; BL00291
gp; PFAM; PF00377 prion
bb;
gr; 1. STAHL, N. AND PRUSINER, S.B.
gr; Prions and prion proteins.
gr; FASEB J. 5 2799-2807 (1991).
gr;
gr; 2. BRUNORI, M., CHIARA SILVESTRINI, M. AND POCCHIARI, M.
gr; The scrapie agent and the prion hypothesis.
gr; TRENDS BIOCHEM.SCI. 13 309-313 (1988).
gr;
gr; 3. PRUSINER, S.B.
gr; Scrapie prions.
gr; ANNU.REV.MICROBIOL. 43 345-374 (1989).
bb;
gd; Prion protein (PrP) is a small glycoprotein found in high quantity in the brain of animals infected with
gd; certain degenerative neurological diseases, such as sheep scrapie and bovine spongiform encephalopathy (BSE), gd; and the human dementias Creutzfeldt-Jacob disease (CJD) and Gerstmann-Straussler syndrome (GSS). PrP is
gd; encoded in the host genome and is expressed both in normal and infected cells. During infection, however, the gd; PrP molecules become altered and polymerise, yielding fibrils of modified PrP protein.
gd;
gd; PrP molecules have been found on the outer surface of plasma membranes of nerve cells, to which they are
gd; anchored through a covalent-linked glycolipid, suggesting a role as a membrane receptor. PrP is also
gd; expressed in other tissues, indicating that it may have different functions depending on its location.
gd;
gd; The primary sequences of PrP's from different sources are highly similar: all bear an N-terminal domain
gd; containing multiple tandem repeats of a Pro/Gly rich octapeptide; sites of Asn-linked glycosylation; an
gd; essential disulphide bond; and 3 hydrophobic segments. These sequences show some similarity to a chicken
gd; glycoprotein, thought to be an acetylcholine receptor-inducing activity (ARIA) molecule. It has been
gd; suggested that changes in the octapeptide repeat region may indicate a predisposition to disease, but it is gd; not known for certain whether the repeat can meaningfully be used as a fingerprint to indicate susceptibility.
gd;
gd; PRION is an 8-element fingerprint that provides a signature for the prion proteins. The fingerprint was
gd; derived from an initial alignment of 5 sequences: the motifs were drawn from conserved regions spanning
gd; virtually the full alignment length, including the 3 hydrophobic domains and the octapeptide repeats
gd; (WGQPHGGG). Two iterations on OWL18.0 were required to reach convergence, at which point a true set comprising gd; 9 sequences was identified. Several partial matches were also found: these include a fragment (PRIO_RAT)
gd; lacking part of the sequence bearing the first motif,and the PrP homologue found in chicken - this matches
gd; well with only 2 of the 3 hydrophobic motifs (1 and 5) and one of the other conserved regions (6), but has an gd; N-terminal signature based on a sextapeptide repeat (YPHNPG) rather than the characteristic PrP octapeptide.
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