Function of the factor I modules (FIMS) of human complement component C6

In order to elucidate the function of complement component C6, truncated C6 molecules were expressed recombinantly, These were either deleted of the f actor I modules (FIMs) (C6des-748-913) or both complement control protein ( CCP) modules and FIMs (C6des-611-913), C6des-748-913 exhibited approximatel y 60-70% of the hemolytic activity of full-length C6 when assayed for Alter native Pathway activity, but when measured for the Classical Pathway, C6des -748-914 was only 4-6% as effective as C6, The activity difference between C6 and C6des-748-913 for the two complement pathways can be explained by a greater stability of newly formed metastable C5b* when produced by the Alte rnative Pathway compared with that made by the Classical Pathway. The half- lives of metastable C5b* and the decay of I-125-C5b measured from cells use d to activate the Alternative Pathway were found to be about 5-12-fold long er than those same parameters derived from cells that had activated the Cla ssical Pathway. I-125-C5 binds reversibly to C6 in an ionic strength-depend ent fashion, but I-125-C5 binds only weakly to C6des-FIMs and not at all to C6des-CCP/FIMs, Therefore, although the FIMs are not required absolutely f or C6 activity, these modules promote interaction of C6 with C5 enabling a more efficient bimolecular coupling ultimately leading to the formation of the C5b-6 complex.