Thioester-containing proteins (TEPs) form an ancient and diverse family of secreted proteins that play central roles in the innate immune response. Two families of TEPs, complement factors and α2-macroglobulins, have been known and studied in vertebrates for many years, but only in the last decade have crystal structures become available. In the same period, the presence of two additional classes of TEPs has been revealed in arthropods. In this review, we discuss the common structural features TEPs and how this knowledge can be applied to the many arthropod TEPs of unknown function. TEPs perform a wide variety of functions that are driven by different quaternary structures and protein-protein interactions between a common set of folded domains. A common theme is regulated conformational change triggered by proteolysis. Structure-function analysis of the diverse arthropod TEPs may identify not just new mechanisms in innate immunity but also interfaces between immunity, development and cell death.
Keywords: Complement system; Crystallography; Infectious disease; Innate immunity.