Reference: Wayne N, et al. (2010) Modular control of cross-oligomerization: analysis of superstabilized Hsp90 homodimers in vivo. J Biol Chem 285(1):234-41

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Abstract


Homo-oligomeric proteins fulfill numerous functions in all cells. The ability to co-express subunits of these proteins that preferentially self-assemble without cross-oligomerizing provides for controlled experiments to analyze the function of mutant homo-oligomers in vivo. Hsp90 is a dimeric chaperone involved in the maturation of many kinases and steroid hormone receptors. We observed that co-expression of different Hsp90 subunits in Saccharomyces cerevisiae caused unpredictable synthetic growth defects due to cross-dimerization. We engineered super-stabilized Hsp90 dimers that resisted cross-dimerization with endogenous Hsp90 and alleviated the synthetic growth defect. Super-stabilized Hsp90 dimers supported robust growth of S. cerevisiae indicating that dissociation of Hsp90 dimers could be hindered without compromising essential function. We utilized super-stabilized dimers to analyze the activity of ATPase mutant homodimers in a temperature sensitive yeast background where elevated temperature inactivated all other Hsp90 species. We found that ATP binding and hydrolysis by Hsp90 are both required for the efficient maturation of GR and v-src confirming the critical role of ATP hydrolysis in the maturation of steroid hormone receptors and kinases in vivo.

Reference Type
Journal Article
Authors
Wayne N, Lai Y, Pullen L, Bolon DN
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