Assembly of multi-subunit structures

Abstract Many cellular proteins are oligomers of identical or different polypeptides, and in most cases, the biological activity of such proteins depends strictly on their quaternary structure. Modifying the assembly of such homo-oligomeric or hetero-oligomeric proteins could be a very specific and efficient way of drug targeting (1-3). This would be greatly facilitated by knowledge about the structural basis of subunit interface stability and of oligomer assembly mechanisms. The Protein Data Bank of three-dimensional structures now contains more than 2000 entries of oligomeric proteins and a number of very large multisubunit structures have been determined in recent years (Table 1). The folding and assembly pathways of many oligomeric proteins have been characterized over the past three decades (4-6) and equilibrium dissociation and unfolding transitions have been analysed for a number of dimeric and a very few higher-number oligomeric proteins (7, 8).