GroEL–Substrate Interactions Joanna L Feltham, Lila M Gierasch  Cell  Volume 100, Issue 2, Pages 193-196 (January 2000) DOI: 10.1016/S0092-8674(00)81557-3

Figure 1 The GroEL Tetradecamer, Represented Here in a Longitudinal Cut-Away View, Consists of Two Rings Stacked Back-to-Back, Each Containing Seven Subunits The apical, intermediate, and equatorial domains of each subunit are shown in yellow, green, and purple, respectively. GroEL-mediated folding in vitro involves each of the two rings of the GroEL tetradecamer alternately in consecutive steps represented in sequence on the uppermost ring: (1) hydrophobically mediated, high-affinity substrate (blue) binding to an empty ring, (2) binding of ATP and GroES, which releases substrate into the hydrophilic cavity of the cis complex (or Anfinsen cage), (3) ATP hydrolysis, which serves as a timing mechanism that potentiates release of GroES and substrate from the chaperonin, and (4) disassembly of the cis complex with concomitant ATP-driven assembly of a new cis complex on the opposing ring. Substrates that do not fold properly in a single round are released to solvent, but can rebind to GroEL for another try. There is intra-ring allostery, which favors saturation of one ring with ATP, and inter-ring negative allostery, which promotes the next step in the cycle in the opposing ring. Cell 2000 100, 193-196DOI: (10.1016/S0092-8674(00)81557-3)

Figure 2 The Peptide-Binding Site of the GroEL Apical Domain (a) The SBP peptide (cyan)–apical domain (green) structure (Chen and Sigler 1999). (b) Residues of the GroEL apical domain that come within 4 Å of the β hairpin SBP peptide are highlighted in purple. (c) Sites of GroEL mutations that diminish binding to a denatured substrate (Fenton et al. 1994) are indicated in orange. (d) Sites in the apical domain where an attached fluorophore senses binding of denatured protein substrates (Tanaka and Fersht 1999) are illustrated in red, and residues that undergo NMR chemical shift changes when a helical peptide binds (Kobayashi et al. 1999) are highlighted in yellow. Coordinates kindly provided by the Sigler laboratory. Cell 2000 100, 193-196DOI: (10.1016/S0092-8674(00)81557-3)