How do Homodimeric proteins fold and assemble?

Protein folding is an increasingly important field in biomedical research. Tools of physical, chemistry, protein engineering, computer simulation and structural biology have been combined to investigate the folding mechanism of many monomeric proteins. However, a large percentage of proteins, from all organisms, are oligomeric and most commonly homodimers. In recent years, numerous folding studies have been carried out to understand the folding and assembly pathways of multisubunit proteins and homodimers in particular. This review chapter describes the current knowledge on the thermodynamic and kinetic stability, the folding process and subunit association of homodimeric proteins. The experimental design and interpretation of data from equilibrium and kinetic techniques are revised, which provide practical information for determining the folding pathways. In addition, several folding models are discussed ranging from the simplest two-state model to those that involve one or more intermediate conformations. This information is of interest for understanding the folding reaction as well as protein-protein interactions of natural multimeric proteins as well as abnormal complexes implicated in disease.