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139  structures 50  species 2  interactions 100  sequences 5  architectures

Family: Prion (PF00377)

Summary: Prion/Doppel alpha-helical domain

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Prion/Doppel alpha-helical domain Provide feedback

The prion protein is thought to be the infectious agent that causes transmissible spongiform encephalopathies, such as scrapie and BSE. It is thought that the prion protein can exist in two different forms: one is the normal cellular protein, and the other is the infectious form which can change the normal prion protein into the infectious form. It has been found that the prion alpha-helical domain is also found in the Doppel protein.

Literature references

  1. Riek R, Hornemann S, Wider G, Billeter M, Glockshuber R, Wuthrich K; , Nature 1996;382:180-182.: NMR structure of the mouse prion protein domain PrP(121-321). PUBMED:8700211 EPMC:8700211

  2. Riek R, Hornemann S, Wider G, Glockshuber R, Wuthrich K; , FEBS Lett 1997;413:282-288.: NMR characterization of the full-length recombinant murine prion protein, mPrP(23-231). PUBMED:9280298 EPMC:9280298


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR022416

This entry represents the C-terminal beta-ribbon domain found in prion proteins [PUBMED:11524679] and the prion-like Doppel proteins [PUBMED:12595265]. This domain has a beta-alpha-beta-alpha(2) structure that contains an antiparallel beta-ribbon.

Prion protein (PrP-c) [PUBMED:2572197, PUBMED:1916104, PUBMED:2908696] is a small glycoprotein found in high quantity in the brain of animals infected with certain degenerative neurological diseases, such as sheep scrapie and bovine spongiform encephalopathy (BSE), and the human dementias Creutzfeldt-Jacob disease (CJD) and Gerstmann-Straussler syndrome (GSS). PrP-c is encoded in the host genome and is expressed both in normal and infected cells. During infection, however, the PrP-c molecule become altered (conformationally rather than at the amino acid level) to an abnormal isoform, PrP-sc. In detergent-treated brain extracts from infected individuals, fibrils composed of polymers of PrP-sc, namely scrapie-associated fibrils or prion rods, can be evidenced by electron microscopy. The precise function of the normal PrP isoform in healthy individuals remains unknown. Several results, mainly obtained in transgenic animals, indicate that PrP-c might play a role in long-term potentiation, in sleep physiology, in oxidative burst compensation (PrP can fix four Cu2+ through its octarepeat domain), in interactions with the extracellular matrix (PrP-c can bind to the precursor of the laminin receptor, LRP), in apoptosis and in signal transduction (costimulation of PrP-c induces a modulation of Fyn kinase phosphorylation) [PUBMED:12354606].

The normal isoform, PrP-c, is anchored at the cell membrane, in rafts, through a glycosyl phosphatidyl inositol (GPI); its half-life at the cell surface is 5 h, after which the protein is internalised through a caveolae-dependent mechanism and degraded in the endolysosome compartment. Conversion between PrP-c and PrP-sc occurs likely during the internalisation process.

In humans, PrP is a 253 amino acid protein, which has a molecular weight of 35-36 kDa. It has two hexapeptides and repeated octapeptides at the N terminus, a disulphide bond and is associated at the C terminus with a GPI, which enables it to anchor to the external part of the cell membrane. The secondary structure of PrP-c is mainly composed of alpha-helices, whereas PrP-sc is mainly beta-sheets: transconformation of alpha-helices into beta-sheets has been proposed as the structural basis by which PrP acquires pathogenicity in TSEs. The three-dimensional structures shows the protein to be made of a globular domain which includes three alpha-helices and two small antiparallel beta-sheet structures, and a long flexible tail whose conformation depends on the biophysical parameters of the environment. Crystals of the globular domain of PrP have recently been obtained; their analysis suggests a possible dimerisation of the protein through the three-dimensional swapping of the C-terminal helix 3 and rearrangement of the disulphide bond.

Gene Ontology

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Domain organisation

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Alignments

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

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(15)
Full
(100)
Representative proteomes UniProt
(957)
NCBI
(1070)
Meta
(0)
RP15
(16)
RP35
(37)
RP55
(62)
RP75
(89)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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  Seed
(15)
Full
(100)
Representative proteomes UniProt
(957)
NCBI
(1070)
Meta
(0)
RP15
(16)
RP35
(37)
RP55
(62)
RP75
(89)
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  Seed
(15)
Full
(100)
Representative proteomes UniProt
(957)
NCBI
(1070)
Meta
(0)
RP15
(16)
RP35
(37)
RP55
(62)
RP75
(89)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: prion;
Type: Domain
Author: Bateman A, Finn RD
Number in seed: 15
Number in full: 100
Average length of the domain: 115.20 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 51.10 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 26.3 26.1
Noise cut-off 22.7 22.1
Model length: 117
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

V-set Prion

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Prion domain has been found. There are 139 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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