Membrane Attack Complex / MAC: Complement Component C7

Membrane Attack Complex / MAC: Complement Component C7

Membrane Attack Complex / MAC: Complement Component C7 Background

The molecular architecture of human complement component C7 was elucidated at several structural levels. The complete primary structure of C7 was derived from the cDNA sequence of clones isolated from a human liver library. C7 is a mosaic protein that consists of 821 amino acids. The amino-terminal twothirds of C7 has 23-30% homology with complement components C8 and C9. In addition, the carboxyl-terminal third contains four cysteine-rich segments that have overlapping internal homology. The protein is a single polypeptide chain with 28 disulfide bonds and is glycosylated at two sites. Virtually all the cysteines are found in small units of 35-77 amino acids that exhibit homology with those of various proteins including the low density lipoprotein receptor, epidermal growth factor precursor, thrombospondin, and blood coagulation factors IX and X.

Using a radioiodinated photoreactive cross-linking reagent bound to the polar head group of phosphatidylethanolamine, the stalk part of the C5b-7 complex could be labeled preferentially, and it was found to consist mainly of C6 and C7. Thus,C7 plays a major role in bringing about the hydrophilic-amphiphilic transition during the formation of the membrane attack complex, and it serves as a membrane anchor for the C5b-7 complex.

C7 is one of five precursor proteins of the membrane attack complex (MAC) of complement. Assembly of the MAC on target cells leads to the formation of transmembrane pores which cause impairment of the membrane permeability barrier and eventual cell death. The MAC is formed, following enzymatic cleavage of C5, by the sequential fusion of C5b, C6, C7, C8, and C9. Fusion is accompanied by a hydrophilic-amphiphilic transition of the proteins and results in the generation of an integral membrane protein complex. C7 fulfills a crucial role in the hydrophilic-amphiphilic transition because it confers on the intermediate complex C5b-7 the transient ability to bind directly to the target cell membranes. The membrane-bound C5b-7 complex enables C8 and C9 to insert themselves into the target membrane and to form a transmembrane pore.

Membrane Attack Complex / MAC: Complement Component C7 References

1. DiScipio R G, et al. (1988). The structure of human complement component C7 and the C5b-7 complex. Journal of Biological Chemistry, 263(1), 549-560.