Factor B of the complement system is a five-domain, 90 kD serine protease proenzyme which is activated by the protease factor D in the context of the Mg2+-dependent complex C3bB during complement activation. The cleavage of factor B into the Ba and Bb fragments during activation facilitates the assembly of the alternative pathway C3 convertase, C3bBb. The Ba fragment contains three short consensus repeat (SCR) domains, while the Bb fragment contains a von Willebrand factor type A (vWF-A) domain and a serine protease (SP) domain. All the domain types of factor B have been implicated in interactions with activated C3 and the assembly of the alternative pathway C3 convertase. This thesis describes a number of structural and functional studies using six different preparations of factor B and its fragments and domains. Surface-enhanced laser desorption-ionization affinity mass spectrometry (SELDIAMS) was used to investigate the reaction of factor B with immobilised activated C3(NH3) in the presence of Mg2+. From this it was determined that (i) a major function of the vWF-A domain is to bind to activated C3 during the formation of the C3 convertase, which it does at its active site cleft, and that (ii) SELDIAMS provides an efficient means of identifying residues involved in protein-protein interactions. Next, 1H NMR, FTIR and circular dichroism spectroscopy studies were performed to provide unequivocal evidence to confirm that the factor B vWF-A domain has allosteric properties and the conformation is dependent upon the presence of bound metal. This implies that the vWF-A interaction with C3b may alter its Mg2+-bound coordination. Further 1HNMR spectroscopic evidence is presented to confirm that the solution structure of factor B was not in an extended arrangement, but its five domains were involved in close interactions. It is proposed that the conformation of the Ba fragment is affected by its incorporation into factor B. The Ba fragment is involved in decoupling an interaction between the vWF-A and SP domains and the proximity of the vWF-A and SP domains within the Bb fragment leads to a conformational change in which conserved charged residues may be important. Allosteric structural rearrangements in the SP domain as the result of its interactions with the vWF-A domain or the Ba fragment provide an explanation of the regulation of the catalytic activity of factor B.