Abstract
CHAPERONINS are ring-shaped protein complexes that are essential in the cell, mediating ATP-dependent polypeptide folding in a vari-ety of compartments1–3. Recent studies suggest that they function through multiple rounds of binding and release of non-native proteins: with each round of ATP-driven release into the bulk solution, a substrate protein kinetically partitions between folding to the native state or rebinding to another chaperonin molecule4–6. To gain further insight into the mechanism of polypeptide binding and release by the chaperonin GroEL from Escherichia coli, we have undertaken a mutational analysis that relates the functional prop-erties of GroEL to its crystal structure7. Our functional tests iden-tify a putative polypeptide-binding site on the inside surface of the apical domain, facing the central channel, consisting of hydropho-bic residues. These same residues are essential for binding of the co-chaperonin GroES, which is required for productive polypeptide release. A highly conserved residue, Asp 87, positioned within a putative nucleotide-binding pocket in the top of the equatorial domain, is essential for ATP hydrolysis and polypeptide release.
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Fenton, W., Kashi, Y., Furtak, K. et al. Residues in chaperonin GroEL required for polypeptide binding and release. Nature 371, 614–619 (1994). https://doi.org/10.1038/371614a0
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DOI: https://doi.org/10.1038/371614a0
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