Chaperones substrate binding site

Wickner, S. and Maurizi, M. R. Here s the hook similar substrate binding sites in the chaperone domains of Clp and Lon. 

The allosteric coupling between the nucleotide binding site and the substrate binding site of Hsp70 chaperone protein. 

Fig. 5. Model for sHsp chaperone activity. The sHsp oligomer (T Hspl6.9 shown here) is in rapid equilibrium with a smaller species (possibly a dimer). Heat-denatured substrates bind hydrophobic sites exposed on the sHsp subunits to form soluble sHsp/substrate complexes, preventing formation of insoluble aggregates of denatured proteins. The sHsp/substrate complexes may also be in rapid equilibrium, and when dissociated, the denatured substrate can be picked up and refolded in an ATP-dependent fashion by the Hsp70 or DnaK (plus cochaperone) machinery. Note that sHsp/substrate complexes can also become larger and insoluble, and the fate of these latter complexes is unknown.

Fig. 5. Copper homeostasis in Enterococcus hirae. Under copper-limiting conditions, copper is pumped into the cell by CopA. The CopZ copper chaperone picks up copper at this site of entry. Under physiological copper conditions, Zn(II)CopY binds to the promoter and represses transcription of the cop operon. Under conditions of copper excess, Cu-CopZ donates Cu(I) to CopY, which leads to the replacement of the Zn(II), loss of DNA-binding affinity, and ultimately synthesis of the operon products. Excess copper is secreted by the CopB efflux pump. The substrate for this pump may be a copper-glutathione (GSH) complex, rather than Cu-CopZ.

Figure 11 Pharmacological chaperones (grey triangles) bind to the active site of a protein, misfolded due to a mutation (black ellipse) and restore the functional protein conformation. Thus the protein is prevented from early degradation. The stable chaperone-protein complex is transferred by the endoplasmic reticulum vesicles to the Golgi and later to the lysosome, where the inhibitor is replaced by the natural substrate.

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