Problems with aggregated proteins

When attempting to use NMR to measure a dissociation constant, the basic experiment will be to vary the ligand concentration in the presence of a fixed concentration of protein. (The converse experiment, varying the protein concentration, may sometimes be carried out, but is generally less satisfactory because of problems with protein solubility and aggregation.) What one sees in this experiment will depend critically on the rate of... 

Aggregration is a problem for unfolded proteins because the hydrophobic residues, which normally are deep inside of a protein, may be exposed when the protein is released from the ribosome. If they are exposed to hydrophobic residues in other strands, the two strands may associate with each other hydrophobically (to aggregate) instead of folding properly. The GroEL-ES complex from E. coli is one such chaperone system. It provides a central cavity in which new protein chains can be "incubated" until they have folded properly (Figure 6.26). 

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