Zenthon, J.F. and Ness, F. and Cox, B. and Tuite, M.F. (2006) The [PSI+] prion of Saccharomyces cerevisiae can be propagated by an Hsp104 orthologue from Candida albicans. Eukaryotic Cell, 5 (2). pp. 217-225. ISSN 1535-9778.
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The molecular chaperone Hsp104 is not only a key component of the cellular machinery induced to disassemble aggregated proteins in stressed cells of Saccharomyces cerevisiae but also plays an essential role in the propagation of the [PSI+], [URE3], and [RNQ/PIN+] prions in this organism. Here we demonstrate that the fungal pathogen Candida albicans carries an 899-residue stress-inducible orthologue of Hsp104 (CaHsp104) that shows a high degree of amino acid identity to S. cerevisiae Hsp104 (ScHsp104). This identity is significantly lower in the N- and C-terminal regions implicated in substrate recognition and cofactor binding, respectively. CaHsp104 is able to provide all known functions of ScHsp104 in an S. cerevisiae hsp104 null mutant, i.e., tolerance to high-temperature stress, reactivation of heat-denatured proteins, and propagation of the [PSI+] prion. As also observed for ScHsp104, overexpression of CaHsp104 leads to a loss of the [PSI+] prion. However, unlike that of ScHsp104, CaHsp104 function is resistant to guanidine hydrochloride (GdnHCl), an inhibitor of the ATPase activity of this chaperone. These findings have implications both in terms of the mechanism of inhibition of Hsp104 by GdnHCl and in the evolution of the ability of fungal species to propagate prions.
|Additional information:||1535-9778 (Print) Journal Article Research Support, Non-U.S. Gov't|
|Uncontrolled keywords:||Amino Acid Sequence Candida albicans/drug effects/*metabolism Fungal Proteins/chemistry/*metabolism Gene Expression Regulation, Fungal Genetic Complementation Test Guanidine/pharmacology *Heat-Shock Proteins Hyperthermia, Induced Molecular Sequence Data Prions/*metabolism Saccharomyces cerevisiae/cytology/genetics/*metabolism Saccharomyces cerevisiae Proteins/*metabolism Sequence Alignment Subcellular Fractions|
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences > Protein Science Group|
|Depositing User:||Mick Tuite|
|Date Deposited:||02 Sep 2008 23:13|
|Last Modified:||14 Jan 2010 14:20|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/5450 (The current URI for this page, for reference purposes)|
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