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Vol. 10, Issue 11, 3623-3632, November 1999

The Cytoplasmic Chaperone Hsp104 Is Required for Conformational Repair of Heat-denatured Proteins in the Yeast Endoplasmic Reticulum

Anna-Liisa Hänninen,^* Mari Simola,^* Nina Saris,^* and Marja Makarow^*

 ^*Institute of Biotechnology, University of Helsinki, Helsinki, Finland; and  Department of Biochemistry, Faculty of Medicine, University of Kuopio, Kuopio, Finland

Severe heat stress causes protein denaturation in various cellular compartments. If Saccharomyces cerevisiae cells grown at 24°C are preconditioned at 37°C, proteins denatured by subsequent exposure to 48-50°C can be renatured when the cells are allowed to recover at 24°C. Conformational repair of vital proteins is essential for survival, because gene expression is transiently blocked after the thermal insult. Refolding of cytoplasmic proteins requires the Hsp104 chaperone, and refolding of lumenal endoplasmic reticulum (ER) proteins requires the Hsp70 homologue Lhs1p. We show here that conformational repair of heat-damaged glycoproteins in the ER of living yeast cells required functional Hsp104. A heterologous enzyme and a number of natural yeast proteins, previously translocated and folded in the ER and thereafter denatured by severe heat stress, failed to be refolded to active and secretion-competent structures in the absence of Hsp104 or when an ATP-binding site of Hsp104 was mutated. During recovery at 24°C, the misfolded proteins persisted in the ER, although the secretory apparatus was fully functional. Hsp104 appears to control conformational repair of heat-damaged proteins even beyond the ER membrane.

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   Corresponding author. E-mail address: marja.makarow{at}helsinki.fi.

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Molecular Biology of the Cell
Vol. 10, 3623-3632, November 1999
Copyright © 1999 by The American Society for Cell Biology

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