Prion protein

The prion protein (PrP) is a cell surface glycoprotein. PrP can exist in two alternatively folded confirmations: the cellular isoform (PrP^C) can undergo a structural conversion to a 'scrapie' or disease associated isoform termed PrP^Sc. 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^Sc, which arise from autocatalytic refolding of PrP^C in a template-dependent manner.

Structure of PrP^CStructure of PrPC

spinqualitylabelsall models PDB ID 1hjm Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
1hjm, 1 NMR models ()
Related:	1e1g, 1e1j, 1e1p, 1e1s, 1e1u, 1e1w, 1hjn
Structural annotation: Resources: CATH : 1Hjma00 InterPro : Ipr000817 Pfam : PF00377 SCOP : d1hjma_ UniProt : P04156
Functional annotation: Cellular component: extrinsic to membrane plasma membrane Golgi apparatus membrane raft cytoplasm membrane endoplasmic reticulum Biological process: protein homooligomerization cellular copper ion homeostasis metabolic process response to oxidative stress Molecular function: copper ion binding protein binding GPI anchor binding tubulin binding microtubule binding
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

PrP^C has a natively unstructured N-terminal region, and a predominantly α-helical C-terminal region from residues ~120-230, with a single disulfide bond. The presence of the N-terminus has little impact on the structure of the C-terminal domain .

The structure is highly conserved amongst mammals, and only differs slightly in birds, reptiles and amphibians.

ALthough having a similar overall fold, the X-ray structure of sheep PrP was dimeric

Models of PrP^Sc structureModels of PrPSc structure

Circular dichroism studies first demonstrated that PrP^Sc had very different proportions of α-helices and β-sheet to PrP^C

There are a number of technical obstacles in determining the molecular structure of PrP(sup)Sc

Genetic prion diseasesGenetic prion diseases

A number of mutations in PrP have been identified which correlate with a high incidence of prion disease. The structure of HuPrP,E200K was determined nd shown to be To date, structural studies of all mutant PrP^C have extremely similar structures to wild type PrP^C, suggesting a kinetic basis for the difference in converting to PrP^Sc.

Prion strainsPrion strains

The strain phenomenon of prions ( ) was initially difficult to equate with the

Selected PrP structuresSelected PrP structures

All structures determined by NMR unless otherwise specified

Human PrPHuman PrP

• 1qlx HuPrP residues 23-230
• 1qm0 HuPrP residues 90-230
• 1qm2 HuPrP residues 121-230
• 1i4m HuPrP residues 119-226 (determined by X-ray crystallography)
• 1fkc HuPrP,E200K residues 90-231 (genetic prion disease)
• 1h0l HuPrP residues 121-230, with an additional disulphide bond analogous to the homolog Doppel

Other species PrPsOther species PrPs

• 1xyx Mouse PrP residues
• 1b10 Syrian hamster PrP residues 90-231
• 1dwy Cow PrP residues 121-230
• 1uw3 Sheep PrP (determined by X-ray crystallography)
• 1xu0 Frog PrP residues 98-226
• 1u3m Chicken PrP
• 1u5l Turtle PrP residues 121-226

ReferencesReferences

Zahn, R. et al. (2000) NMR solution structure of the human prion protein Proc. Natl. Acad. Sci. USA 97, 145-150 Zahn R. et al. (2003) NMR structure of a variant human prion protein with two disulfide bridges J. Mol. Biol. 326, 225-34.