Self-association of the seventh component of human complement (C7): dimerization and polymerization.
Two association reactions of isolated C7 are described. The incubation of isolated C7 in 1% deoxycholate results in hemolytically inactive dimeric C7 that has a sedimentation coefficient of 7.3S. Dimeric C7 expressed hydrophobic domains that bound 41 +/- 4 mol deoxycholate per mol C7 and that aggregated upon removal of the detergent. The dimeric nature of the deoxycholate-treated C7 was demonstrated by analytical ultracentrifugation and by gel filtration, and yielded the following parameters: Mr = 230,000; diffusion coefficient, D = 2.9 X 10(-7) cm2/sec, and Stokes' radius, rH = 7.3 nm. Dimeric C7 exhibits an increased electrophoretic mobility and an increased beta-sheet structure, as compared with monomeric C7. Upon incubation with deoxycholate-phospholipid mixed micelles and removal of the detergent, the dimeric C7 became firmly associated with the lipid vesicles and was partially aggregated in the lipid bilayer. Trypsin treatment released approximately 50% of the protein material from the C7 vesicle complex. The other association reaction of isolated C7 occurs upon incubation with 1 M guanidine HC1; C7 forms soluble, linear protein polymers that have sedimentation coefficients ranging from 20 to 30S. The strands are 5 to 8 nm wide and vary in length between 20 to 100 nm. They tend not to aggregate, they are hemolytically inactive, and they exhibit increased beta-sheet structure, as compared with monomeric C7. They can be dissociated to hemolytically active monomers by exposure to 4 M guanidine HC1 and by subsequent 100-fold dilution with buffer. Isolated C5 or C6 did not exhibit any of these properties. The results suggest that the properties acquired by C7 in the hydrophilic-amphiphilic transition may be responsible for the expression of the membrane binding site of "metastable" C5b-7 and for the polymerization of C5b-7 within the target membrane.
D003167:Complement Activation / Q000187:drug effects; D003184:Complement C7 / Q000032:analysis / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000494:pharmacology; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008051:Lipid Bilayers / Q000378:metabolism; D046911:Macromolecular Substances; D008970:Molecular Weight; D010743:Phospholipids / Q000378:metabolism
D003184:Complement C7; D006146:Guanidines; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D010743:Phospholipids; D003840:Deoxycholic Acid; D019791:Guanidine