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

PrP^C 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

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

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...

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. 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 (X-ray)
• 1E1J HuPrP,M166V residues 125-228
• 1E1S HuPrP,S170N residues 125-228
• 1E1W HuPrP,R220K residues 125-228
• 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

• XXXX Mouse PrP R
• 1B10 Syrian hamster PrP residues 90-231
• 1DWY Cow PrP residues 121-230
• 1UW3 Sheep PrP (X ray)
• XXXX Frog PrP
• XXXX Chicken PrP
• XXXX Turtle PrP