Structure and activation of C1, the complex initiating the classical pathway of the complement cascade

Significance The complement system is an essential arm within the innate immune defense. Complement contributes to elimination of objects presenting danger signals such as pathogens, dying host cells, and abnormal molecular structures and is capable of inducing an inflammatory response stimulating further immune responses. The C1 complex is a giant proteolytic enzyme, which plays a leading role, because it is the first component in a proteolytic cascade initiated when complement is activated. On the basis of structural characterization of the C1 complex with X-rays and electron microscopy, we suggest that the first proteolytic reaction in the cascade, activation of the C1 complex itself, involves neighboring C1 complexes located near each other rather than a reaction within individual C1 complexes.