Yeast chaperone Hsp104 and the role in[PSI+ ] prion propagation and elimination

Abstract

Molecular chaperone Hsp104, also known as heat shock protein in yeast Saccharomyces cerevisiae, plays an essential role in thermotorelance response enabling yeast cell survival at high temperature. Hsp104 mediates the misfolding and the aggregation of denatured proteins to refold to their native forms. In addition, it has also reported that Hsp104 protein is required to maintain and propagate the prion state within yeast cells. A prion is an unusual form of protein or misfolded protein and prone to aggregate as large protein polymers. Yeast prion can be transmitted from cell to cell like prions found in humans but does not cause disease. Several studies have revealed that Hsp104 is involved in yeast [PSI+] prion propagation by dissolving prion polymer into the smaller molecules needed to generate a new round of propagation via the same mechanism of Hsp104 in promoting proteins refolding. Interestingly, over-expression of Hsp104, results in elimination of the [PSI+] prion from yeast cells but the mechanism remains unclear. Therefore, it is necessary to gain insight into the mechanism of how elevated Hsp104 induces [PSI+] loss. Furthermore, this information might lead to further treatment of human neurodegenerative diseases caused by misfolding and accumulation of abnormal proteins in the brain.

Keywords

• hsp104
• [psi+ ] prion
• yeast