Ultrastructure of the membrane attack complex of complement. Heterogeneity of the complex caused by different degree of C9 polymerization.
The membrane attack complex (MAC) of complement and its precursors, i.e. C5b-7 and C5b-8, were examined by electron microscopy. C5b-7 bound to lipid vesicles exhibits an extended structure of 25 nm connected to the lipid membrane via a 10-nm long, 3-nm wide stalk. Binding of C8 to vesicle-bound C5b-7 results in the disappearance of this stalk, whereas the overall length remains unchanged. Addition of 12 C9 molecules per C5b-8 induces C9 polymerization which is accompanied by the formation of C9 tubules and membrane lesions. By using biotinyl precursors and streptavidin -coated colloidal gold particles, C5b-6, C7, and C8 was found to be in the club-like part of the MAC; C9 was identified in the tubular moiety. Only one C5b-8 moiety was detected in an individual MAC complex thus excluding the proposed "dimeric" structure of the MAC. A membrane channel of 10 nm was formed by the MAC at a C9 to C5b-8 ratio equal or larger than 12 to 1, as suggested by the penetration of negative stain into the vesicle. In contrast, binding of an average of three C9 per C5b-8 caused formation of incomplete C9 tubules with apparent membrane channels of less than 10 nm diameter. The MAC isolated from red blood cells was ultrastructurally heterogenous . Although an excess of serum was used for the formation of the complexes, mostly incomplete poly C9 tubules were formed. It is proposed that the MAC is an ultrastructurally heterogenous complex that induces the formation of membrane channels of different sizes.
D000818:Animals; D003186:Complement C9 / Q000032:analysis*; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000032:analysis*; D003840:Deoxycholic Acid; D004912:Erythrocytes / Q000276:immunology; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D011108:Polymers / Q000032:analysis; D011817:Rabbits
D003186:Complement C9; D015938:Complement Membrane Attack Complex; D046911:Macromolecular Substances; D011108:Polymers; D003840:Deoxycholic Acid; D003165:Complement System Proteins