Fwd: [MC_USA] Prions in Yeast

[Guest guest]

MC_USA

Wayne Fugitt

Mon, 05 Jan 2004 23:20:08 -0600

[MC_USA] Prions in Yeast

 

Prions in Yeast

 

Two proteins in yeast (Saccharomyces cerevisiae)

· the Sup35 protein ( " Sup35p " ) and

· the Ure2 protein (Ure2p)

are able to form prions; that is, they can exist either

· in a PrPC-like form that is functional or

· in a PrPSc-like form that is not.

 

The greater ease with which yeast can be studied has

 

· proved that only protein is involved in prion formation and

· provided insight into the need for PrPSc to find PrPC molecules of a

similar primary structure in order to be able to convert them into the

PrPSc form.

Evidence that prions are a " protein-only " phenomenon

· A few molecules of a PrPSc form of the Sup35 protein, when introduced

into yeast cells, convert the yeast cell's own Sup35 protein into prion

aggregates. The resulting " disease " phenotype is then passed on to the cell's

daughters.

The introduced protein was synthesized in bacteria making it unlikely that it

could be contaminated by any gene-containing infectious agent of yeast.

 

· Yeast can be " cured " of their prion " disease " by increasing the activity

of their · chaperones. Presumably the chaperone helps maintain the folded

state (with alpha helices) of the protein.

 

· When the gene for the · glucocorticoid receptor is altered to include

sequences coding for one part (domain) of the Sup35 protein, the resulting

protein forms prions and produces an entirely new phenotype.

 

Possible basis of species specificity of prions

 

· A particular PrPSc can only convert PrPC molecules of the same - or at

least similar - primary structure.

· This requirement of " like-with-like " resides in a short sequence at the

· N-terminal of the protein (rather like an antibody · epitope).

 

· Yeasts engineered to form two types of prion form two types of " pure "

aggregates within the cell.

· Even in the test tube, each type of prion finds and aggregates with

others of its own type.

 

So the picture that emerges is that a molecule of PrPSc

· acts as a " seed " providing a template for converting PrPC to more PrPSc

· These interact with each other to form aggregates.

 

Although only a small portion of the prion protein is responsible for its

specificity, other parts of the molecule are needed for flipping the molecule

from the alpha-helical to the beta conformation. All prion proteins contain

tracts of repeated Gln-Asn residues which appear to be essential for the

conversion process.

The deposits of PrPScin the brain are called amyloid. Amyloid deposits are also

found in other diseases involving the brain, such as Alzheimer's disease.

 

Most cells, including neurons in the brain, contain proteasomes that are

responsible for degrading misfolded or aggregated proteins. In the various brain

diseases characterized by a build-up of amyloid deposits, it appears that the

amount of amyloid overwhelms the capacity of the proteasomes to do their job.

Because of the critical role of proteasomes in other cell functions, such as

mitosis, it is easy to see why these deposits lead to death of the cell.

 

If you want to see an antimated GIF of molecule combining, and more related

topics, use the link

below. ( also a few embedded links will work from the page below )

 

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Prions.html#YeastPrions