One of these proteins, Hsp90, is particularly abundant, comprising 1-2% of all proteins in a cell. Yet, under normal conditions, a cell uses only about 10% of its Hsp90, leaving a large reservoir of its function available should conditions suddenly turn more stressful.
Over the past several years, Lindquist has built the case that this Hsp reservoir is responsible for substantial evolutionary changes in relatively short periods of time. Her lab has shown that the pathogenic Candida albicans and Aspergillus fungi rely on Hsp90 to evolve drug-resistance. Cancer cells often exploit the Hsps' function to support carcinogenic proteins. Earlier research has also shown that selective breeding can enrich variation responsible for these phenotypes, allowing an Hsp90-reliant trait to be inherited even in the absence of stress.
The Hsp90 buffer appears to function in two ways with mutant proteins: either to mask or reveal the phenotypic consequences of mutations. In the first case, Hsp90 braces mutant proteins into "normal" shapes, thereby hiding the mutant proteins' traits. As conditions become increasingly stressful, the Hsp90 buffer must act on more and more proteins. At a certain point, the Hsp90 buffer becomes overwhelmed, and the mutant proteins' traits are exhibited.
In the second scenario, proteins that are not functional on their own are shaped into working forms. These mutant proteins cannot perform their jobs withou
|Contact: Nicole Giese|
Whitehead Institute for Biomedical Research