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pubmed:abstractText |
Activation of the classical complement (C) system involves conversion of C1 to its active state with subsequent cleavage of C4 and -d C2 so as to form the classical C3 convertase, C42 (a bar indicates the activated form of a protein), which sequentially cleaves C3 and C5 to initiate the cytolytic event associated with the complete reaction. An alternative, pr properdin-dependent, pathway to complement activation generates a C3 convertase, C3B, that is formed by cleavage of B with D in the presence of a C3b, the major cleavage fragment of C3. C3b is capable of binding activated properidin (P) with resultant stabilization of C3B, which otherwise rapidly decays by loss of B activity. Initial cleavage of C3, a prerequisite for formation of C3B, is demonstrated to occur through the interaction of native C3 and B in the presence of either D or P alone, or together. The effect of P on the interaction of D, B, and C3 is attributed to stabilization of C3B as has been shown for C3B. Larger amounts of P and B with C3 in the absence of D form a C3 convertase that is designated (P)C3B to indicate that demonstrable cleavage of B does not occur although the active site is available. The generation of this initial convertase, as assessed by C3 inactivation, is dose-related to P and B inputs. The presence of both P and D greatly augments initial cleavage of C3 with D fully uncovering the active site of B and P stabilizing that site.
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