The unfolding action of GroEL on a protein substrate

A mol. dynamics simulation of the active unfolding of denatured rhodanese by GroEL mol. chaperone (chaperonin) is presented.  The compact denatured protein was bound initially to the cis cavity and formed stable contacts with several of the subunits.  As the cis ring apical domains of GroEL underwent the transition from the closed to the more open (ATP-bound) state, they exerted a force on rhodanese that led to the increased unfolding of certain loops.  The contacts between GroEL and rhodanese were analyzed and their variation during the GroEL transition was shown.  The major contacts, which gave rise to the stretching force, were found to be similar to those obsd. in crystal structures of peptides bound to the apical domains.  The results of the simulation showed that multidomain interactions play an essential role, in accord with expts.  Implications of the results for mutation expts. and for the action of GroEL are discussed.