ABSTRACT
This chapter describes the structures of human C3d and C4d of the C4A isotype. The backbone structures of these two fragments turned out to be much more similar than one would have predicted based on sequence similarity, for the most part the structures will be presented in a compare and contrast manner. The chapter summarizes insights gained from inspection of the C3d and C4Ad structures have prompted some functional studies. The catalyzed versus noncatalyzed transacylation mechanisms also explain why the competing water hydrolysis reactions are much faster for C4B than for C4A. To protect the thioester from large-scale spontaneous hydrolysis in the native molecule, it must be sequestered from the surface and only become surface exposed following proteolytic activation of C3 and C4. A comparison of the structures of C3d and C4Ad in the thioester and isostypic regions suggests a mechanism for such a rate difference in acylimadazole formation.
