GroEL-GroES ATP-directed reaction cycle
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At physiological concentrations of ATP, ~1mM, GroEL binds ATP cooperatively
within the seven sites of one ring.
At this concentration of ATP, the opposite ring will not become occupied with
ATP (anticooperative behavior between rings).
The polypeptide is normally accepted into the open ring of a trans ADP
asymmetric complex. ATP most likely has reached the open ring before
polypeptide binding.
Binding of ATP in the open ring produces a movement of the polypeptide-binding
apical domains of GroEL.
This renders the ring competent to bind GroES, whose association is accompanied
by further movements of the apical domains of GroEL.
Since GroES lid binding is dependent upon ATP binding, the lid will rapidly bind
to the ATP-occupied ring.
The binding of GroES removes the hydrophobic polypeptide-binding sites from
facing the cavity allowing release of the polypeptide substrate into a nowencapsulated hydrophilic cis cavity where folding commences. The cis cavity is
rich in hydrophilic residues.
Folding continues in the cis cavity during what is the longest phase of the reaction
cycle, ~10 s, before ATP hydrolysis in the cis ring weakens the affinity of GroEL
for GroES and gates the entry of ATP into the sites of the opposite, so-called
trans ring.
The binding of ATP in trans sends an allosteric signal that ejects the cis ligands:
GroES; substrate protein, whether folded or not; and ADP.
ATP binding in the trans ring enables binding of GroES to that ring, triggering a
further round of cis folding.
Thus, the two rings switch back and forth, employing one ring of seven ATPs to
discharge an old folding-active ring while simultaneously nucleating a new one.