Abstract
The acquisition of spatial structure in proteins may be described in terms of hierarchical condensation, with contributions of local interactions between next neighbours and the interactions between domains and subunits accumulating to create the marginal free energy of stabilization characteristic of the functional state of globular proteins. Domains represent independent folding units such that the overall kinetics divide into the sequential collapse of subdomains and domains and their merging to form the compact tertiary structure. In proceeding to oligomeric proteins, docking of subunits follows the formation of structured monomers. Thus, the overall mechanism of folding and association obeys consecutive uni-bimolecular kinetics. Beyond a limiting protein concentration, aggregation will outrun proper domain pairing and subunit association. In the cell, accessory proteins are involved in catalysis of the rate-determining steps of folding (proline isomerization and SH-SS exchange) and in the kinetic partitioning between folding and aggregation (chaperone action). The practical aspects of accessory proteins have been investigated in detail using immunotoxins and antibody fragments as examples. Additional concepts allowing off-pathway reactions in protein reconstruction to be kept to a minimum refer to pulse-dilation, reverse micelles and immobilization of polypeptide chains on matrices.
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology
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