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Eukaryotic Cell, February 2006, p. 217-225, Vol. 5, No. 2
1535-9778/06/$08.00+0     doi:10.1128/EC.5.2.217-225.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The [PSI⁺] Prion of Saccharomyces cerevisiae Can Be Propagated by an Hsp104 Orthologue from Candida albicans

Joanna F. Zenthon, Frederique Ness, Brian Cox, and Mick F. Tuite^*

Protein Science Group, Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom

Received 23 August 2005/ Accepted 26 October 2005

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.

Present address: L.B.M.S.-UMR-CNRS 5095, Universite Victor Segalen, Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux, France.