Location of Different Binding Sites in C 3 Fragments

T h e third c o m p o n e n t of complemen t (C) ~ has a central role in the activation of both the classical and al ternat ive pathways. C3 also has a variety o f di f ferent functions that are expressed e i ther a f ter C3 activation or dur ing the normal b reakdown o f the molecule. These functions of C3 are dependen t upon the exposure within C3 o f binding sites for o ther se rum proteins or for m e m b r a n e C3 receptors . None o f these binding sites is available in native C3 (1, 2), and each type of binding site is exposed only dur ing C3 activation and subsequent f ragmenta t ion . T h e s t ructure and funct ion o f the di f ferent C3 f ragments and the mechanism o f their genera t ion has been a subject o f intense research af ter initial repor ts that inactivated C3b (iC3b) expressed functions that were distinct f rom those of C3b (3, 4). Recent studies have now demons t ra t ed that factor I is the p r imary enzyme responsible for the normal physiologic b reakdown of C3b (5-7). T h e key to defining the pathway of I cleavage of C3b was the demons t ra tion that two different cofactors are requi red for l cleavage of C3b and iC3b (6,