The structure and function of protein modules.

Analysis of protein sequences shows that many proteins in multicellular organisms have evolved by a process of exon shuffling, deletion and duplication. These exons often correspond to autonomously folding protein modules. Many extracellular enzymes have this modular structure; for example, serine proteases involved in blood-clotting, fibrinolysis and complement. The main role of these modules is to confer specificity by protein-protein interactions. Lack of structural information about such proteins has required a new strategy for studying the structure and function of protein modules. The strategy involves the production of individual modules by protein expression techniques, determination of their structure by high resolution nuclear magnetic resonance and definition of functional patches on the modules by site-directed mutagenesis and biological assays. The structures of the growth factor module, the fibronectin type 1 module and the complement module are briefly described. The possible functional roles of modules in various proteins, including the enzymes factor IX and tissue plasminogen activator, are discussed.