The reaction cycle of groe-assisted protein folding - Texas A&M University (TAMU) Scholar

Chaperonins are double-ring assemblies that mediate ATP-dependent folding of a large variety of polypeptides. Recent studies of the bacterial chaperonin, GroEL, suggest that it provides an environment, its central channel, that assists proper folding, through two actions, associated with specific conformational states. One is the binding of collapsed, partially-structured, folding intermediates in the open central channel, via hydrophobic side chains lining the channel. This forestalls aggregation and may be associated with structural rearrangement amounting to partial unfolding, most likely through multivalent binding by the 7 surrounding subunits. The other action is facilitation of folding, occurring after release of polypeptide into an enlarged, and now hy drophilic, central channel produced upon binding by the cochaperone, GroES, in the presence of ATP. This fol ding-active state has a lifetime of 15-30 sec, after which ATP binding to the opposite ring evicts the GroES and polypeptide ligands. For any substrate protein, a fraction reaches the native state or a conformation committed to it while in the central channel before this "timer" sounds, while the remaining fraction is evicted in a non-native state that can be rebound by other chaperone molecules or proteases. Our recent studies have focused on elucidating how this machine recycles and on identifying its natural substrates.

The reaction cycle of groe-assisted protein folding Academic Article