A yeast-based assay reveals a functional defect of the Q488H polymorphism in human Hsp90{alpha}
- Departement de Biologie Cellulaire, Universite de Geneve, Sciences III, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4 (Switzerland)
It has been argued that the molecular chaperone Hsp90 guards the organism against genetic variations by stabilizing variant Hsp90 substrate proteins. However, little is known about polymorphisms affecting its own functions. We have followed up on a recent study describing two polymorphisms that alter the amino acid sequences of the two Hsp90 isoforms Hsp90{alpha} and Hsp90{beta}. Hsp90 is essential for cell proliferation in the budding yeast Saccharomyces cerevisiae, but the human proteins can replace the endogenous ones. In this growth assay, the variant V656M of Hsp90{beta} was indistinguishable from wild-type. In contrast, the Hsp90{alpha} variant Q488H, which carries an alteration of a very highly conserved residue, was severely defective for growth compared to wild-type Hsp90{alpha}. Hence, the characteristics of this yeast-based system-simplicity, rapidity, low cost-make it ideal for phenotype screening of polymorphisms in HSP90 and possibly many other human genes.
- OSTI ID:
- 20713430
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 337, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2005.09.025; PII: S0006-291X(05)02030-9; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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