Hsp104

Stressors that induce Hsp104 expression include:^[2]

• Heat or cold shock
• Hydrogen peroxide
• Ethanol
• Sodium Arsenide

The role of Hsp104 when interaction with Sup35 Prion Propagation is to interact with polymers. When Hsp104 is elevated it is hypothesized that amyloid polymers can be solubilized in misfolded monomers or intermediates, then later can be refolded into non prion monomers. When there is normal amount of Hsp104 the polymer breaks down into oligomeric "seeds". Low levels of Hsp104 the polymer is not regulates forming aggregates within the cells that can lead to the cells death.^[2]

No fibril formation is seen at a concentration of 1uM of Hsp104. At low concentrations of Hsp104 there is an observed concentration-dependent delay. A lag phase is seen when the Hsp104 concentration is at .01u. This control lag phase being 9 hours but after the low concentration of Hsp104 it is seen to be 72 hours. When the amount of Hsp104 increased the lag phase also increased inhibition of the Fibril formation.^[6]

Hsp104 influences prion inheritance in yeast by remolding amyloids. When this happens, prions infected show a cross-B structure and an amyloid fold.^[7] Hsp104 has a chaperone called Hsp70 in yeast and is dependent for the full efficiency of thermotolerence. When Hsp70 is not accompanied by hsp104 it more useful than if both Hsp's were gone. Hsp70 by itself can only do so much to regulate thermotolerance, Hsp104 is needed when internal levels of Hsp70 are reducing. Hsp104 and Hsp70 also interact to recover native state of proteins that were exposed to heat and formed aggregates. When there is too much Hsp70/40 disaggregation activity by Hsp104 increases. Small heat shock proteins (sHsps) are necessary for Hsp104 by helping with the clearance of aggregates. Some sHsps increase their molecular weight with partially folded proteins and are able to perform disaggregation by Hsp100/ClpB.^[4]