PRE2023-Chaperonas moleculares: un estudio en profundidad de sus estructuras, mecanismos e influencia en diferentes procesos celulares (PID2022-137175NB-I00)

This proposal intends to shed light in the structure and function of a group of proteins termed molecular chaperones, which are involved in protein homeostasis (proteostasis), as they perform a critical role in protein folding, assembly, disaggregation and degradation (Hartl et al., 2011). They include a large number of well-established families (sHsp, Hsp40, Hsp60 or chaperonins, Hsp70, Hsp90, Hsp100, Hsp110) and, almost as important as the chaperones themselves, a large number of cofactors (cochaperones) that direct the complex between the chaperone and the client proteinto the right cellular place and to the proper fate, be it folding, assembly or degradation … All these functions executed by chaperones and cochaperones are somehow coordinated and function like a factory assembly line in which a certain chaperone exerts a particular function to the client and transfers it to another chaperone for the next step in the folding/disaggregation/degradation process. The transient complexes formed by chaperones, cochaperones and clients during these processes are particularly suited for their structural analysis by different cryoelectron microscopy techniques, a branch of electron microscopy that is revolutionizing the structural biology and cell biology fields. This proposal will make use of this and other state-of-the-art techniques at its disposal in the unique infrastructure (at the Spanish level) set up at the Centro Nacional de Biotecnología (CNB) cryoEM facility.