1] Modular design of proteases of coagulation, fibrinolysis, and complement activation: Implications for protein engineering and structure-function studies

Abstract

This chapter focuses on the modular design of proteases of coagulation, fibrinolysis, and complement activation—that is, its implications for protein engineering and structure–function studies. It reviews the evidence supporting the modular evolution of the proteases of blood clotting, fibrinolysis, and complement activation. The chapter also discusses the homologies of plasma proteases—that is, the implications for structure and function. The identification of homologies has greatly facilitated studies on the structure and function of regulatory proteases and other mosaic proteins. The modular assembly hypothesis implies that the gene pieces encoding the modules display a remarkable mobility during evolution: they undergo repeated insertions, tandem duplications, and exchanges. To explain the unusual mobility of these domains, it has been assumed that some special features of their genes contributed to the frequent genetic rearrangements. Exon shuffling is one of the obvious theoretical mechanisms that could be held responsible for module shuffling.