Prion protein: Difference between revisions
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The prion protein (PrP) is a cell surface glycoprotein. | The prion protein (PrP) is a cell surface glycoprotein. PrP can exist in two alternatively folded confirmations: the cellular isoform (PrP<sup>C</sup>) can undergo a structural conversion to a 'scrapie' or disease associated isoform termed PrP<sup>Sc</sup>. Prion diseases such as Creutzfeldt Jakob disease (CJD) in people, and bovine spongiform encephalopathy (BSE) commonly known as "mad cow" disease, are characterterized by aggregates of PrP<sup>Sc</sup>, which arise from autocatalytic refolding of PrP<sup>C</sup> in a template-dependent manner. | ||
=Structure of PrP<sup>C</sup>= | =Structure of PrP<sup>C</sup>= | ||
PrP<sup>C</sup> has a natively unstructured N-terminal region, and a predominantly α-helical C-terminal region from residues ~120-230. | |||
The N-terminal region can bind coper ions | |||
{{STRUCTURE_1hjm | PDB=1hjm | SCENE= }} | {{STRUCTURE_1hjm | PDB=1hjm | SCENE= }} | ||
The structure is highly conserved amongst mammals | The structure is highly conserved amongst mammals, and only differs slightly in birds, reptiles and amphibians. | ||
The X-ray structure of sheep PrP was dimeric... | The X-ray structure of sheep PrP was dimeric... | ||
=Models of PrP<sup>Sc</sup> structure= | =Models of PrP<sup>Sc</sup> structure= | ||
Circular dichroism studies first demonstrated that PrP<sup>Sc</sup> had very different proportions of α-helices and β-sheet to PrP<sup>C</sup> | |||
There are a number of technical obstacles in determining the molecular structure of PrP(sup)Sc</sup> | There are a number of technical obstacles in determining the molecular structure of PrP(sup)Sc</sup> | ||
=Genetic prion diseases= | |||
A number of mutations in PrP have been identified which correlate with a high incidence of prion disease. To date, structural studies of all mutant PrP<sup>C</sup> have extremely similar structures to wild type PrP<sup>C</sup>, suggesting a kinetic basis for the difference in converting to PrP<sup>Sc</sup>. | |||
=Prion strains= | |||
The strain phenomenon of prions ( ) was initially difficult to equate with the | |||
=Selected PrP structures= | =Selected PrP structures= | ||
All structures determined by NMR unless otherwise specified | All structures determined by NMR unless otherwise specified | ||
==Human PrP== | ==Human PrP== | ||
* [[1QLX]] HuPrP | * [[1QLX]] HuPrP residues 23-230 | ||
* [[1QM0]] HuPrP | * [[1QM0]] HuPrP residues 90-230 | ||
* [[1QM2]] HuPrP | * [[1QM2]] HuPrP residues 121-230 | ||
* [[1I4M]] HuPrP | * [[1I4M]] HuPrP residues 119-226 (X-ray) | ||
* [[1E1J]] HuPrP,M166V | * [[1E1J]] HuPrP,M166V residues 125-228 | ||
* [[1E1S]] HuPrP,S170N | * [[1E1S]] HuPrP,S170N residues 125-228 | ||
* [[1E1W]] HuPrP,R220K | * [[1E1W]] HuPrP,R220K residues 125-228 | ||
* [[1FKC]] HuPrP,E200K residues 90-231 (genetic prion disease) | * [[1FKC]] HuPrP,E200K residues 90-231 (genetic prion disease) | ||
* [[1H0L]] HuPrP residues 121-230, with an additional disulphide bond analogous to the homolog Doppel | * [[1H0L]] HuPrP residues 121-230, with an additional disulphide bond analogous to the homolog Doppel | ||
==Other PrPs== | ==Other species PrPs== | ||
* XXXX Mouse PrP | * XXXX Mouse PrP R | ||
* [[1B10]] Syrian hamster PrP 90-231 | * [[1B10]] Syrian hamster PrP residues 90-231 | ||
* [[1DWY]] Cow PrP | * [[1DWY]] Cow PrP residues 121-230 | ||
* [[1UW3]] Sheep PrP (X ray) | * [[1UW3]] Sheep PrP (X ray) | ||
* XXXX Frog PrP | * XXXX Frog PrP | ||
