Scheme 2.

Proposed open-and-close model of the action of the IMC linker. The linker acts as a lid to protect the hydrophobic site against exposure to solvent. At elevated temperatures, the lid (linker) is easily opened with a large dissociation constant, and the protein is prone to aggregate by the adhesion of the hydrophobic site. The addition of extrinsic lid (synthetic linker peptide) can prevent the hydrophobic exposure, and thus rescue the proteins from the aggregation pathway.