Abstract
Incorrect protein folding can lead to many diseases and even aging. Loss of protein function and formation of amyloidogenic protein aggregates are also consequences of protein misfolding. In order to protect these aggregates, many organisms express members of the Hsp100 molecular chaperones family (ClpB in bacteria, Hsp104 in yeast and Hsp101 in plants, for example), which are able to disaggregate other proteins, leading to their reactivation. Surprisingly, metazoan do not have a gene for Hsp100. However, recent studies have shown that a family member of the Hsp110 co-chaperone, along with Hsp70 and Hsp40 chaperones, cooperate in a system with desagregase function. Our research group has already expressed and characterized the human Hsp70 and Hsp40 chaperones, both in structural and functional terms. Recently, we have obtained three cDNAs from the human Hsp110 family members, and only one of these members was tested for desagregase activity. Thus, this project has the aim of investigate the chaperone activity of the other two members not studied yet. Hence, we will clone, express, purify, characterize and test them, both alone and with other chaperones, about the desagregase function. The results have the potential to increase significantly the knowledge about protein homeostasis in the cell, which can generate inputs that have medical and biotechnological application.
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