Conformational Complexity of Complement Component C3

The structures of native C3 and its major fragment C3c have provided a wealth of structural insights into the central protein of the complement system. The proteolytic activation steps, generating the important fragments C3b and iC3b, are thought to induce significant conformational changes in the molecule, yielding protein molecules with distinct binding properties. The structures of C3 and C3c reveal the extent of conformational changes that may be expected. These structures together with the large amount of biochemical, mutagenesis, and binding data available on C3, its fragments, and the various interacting partners provide for the first time a detailed map of the various proposed binding sites. Still, many questions remain unanswered and additional structural data and sitedirected mutagenesis experiments, now made possible in a more rational way, are required to elucidate the complete complexity of the central component of the complement system.