Abstract
The Hsp90 chaperone (heat shock protein 90 kDa) is found in all organisms and in all cellular compartments, and the two types found in the eukaryotic cytosol interact with at least 10% of all proteins produced by the cell. The Hsp90 plays a key role in the maturation of these proteins, which makes it important for many cellular processes such signaling, proteostasis, epigenetics, telomere maintenance, innate immunity, etc. Obviously, changes in this 'highly connected node', as one can label Hsp90, leads to disturbances in cell function resulting in drastic consequences for the organism. For example, Hsp90 appears to play a central role in the pathology of several types of cancer as many kinases are clients and are involved in the development of cancer. As a matter of fact, specific inhibitors of Hsp90 and co-chaperones are under investigation in clinical trials. No human cytosolic Hsp90 had its full three-dimensional structure determined and the mechanisms by which this chaperone functions and is modulated are not yet fully known. Even the set of co-chaperones and post-translational modifications, that play key role in the processes aforementioned, are not yet complete understood. The obvious therapeutic potential that Hsp90 from human, and Hsp90 from other organisms, have, make essential to unravel the forces that stabilize their structure and the mechanisms by which their functions are modulated resulting in the maturation of proteins clients. The importance in studying Hsp90 brought together researchers involved in studying the relationship between structure and function of proteins, particularly chaperones from human, plants and protozoa, that will focus on the following goals: 1) Determination of the conformational aspects of Hsp90, its isolated domains and some of its co-chaperones. 2) Characterization of the ATPase activity of the various types of Hsp90 available. 3) Investigation of the interaction of Hsp90 with several co-chaperones, inhibitors and client proteins. 4) Investigation of the effect that post-translational modifications have in the structure and function of Hsp90. To show our commitment to this proposal we would like to stress that some studies are already underway and already have potential to generate knowledge that is both new and relevant. (AU)
Scientific publications
(26)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
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