Complement component C7 is one of five complement proteins that upon activation of either the classical or the alternative pathway interact sequentially to form a large protein-protein complex, called membrane attack complex (MAC). Assembly of the membrane attack complex (MAC) on target cells results in the formation of transmembrane pores that can lead to killing of the cells. The single polypeptide chain of C7 is composed of 821 amino acid residue, and during the process of membrane attack complex (MAC) formation binds to the C5b6 complex. The resulting C5b-7 complex is transiently endowed with the ability to bind to membrane surfaces. Complement component C7 is structurally similar to the other terminal complement proteins, C6, C8α, C8β, and C9. The genes for C7 as well as those for C6 and C9 are located on chromosome Sp13, while the genes for C8α and C8β are located on the short arm of chromosome 1. The genes for C7 and C6 are 160kb apart and are oriented in a tail-to-tail configuration relative to transcription. The complement component C7 gene has been shown to span about 80 kb of DNA, is encoded by 18 exons, and has an organization very similar to that of the C6 gene.
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. The secondary structural analysis, estimated by circular dichroism, suggested a high content of α-sheet (38%) and β-turns (24%). The tertiary structure, visualized by transmi lipid vesicles was observed to be in the form of monomers or dimers. The monomer C5b-7 consssion electron microscopy, indicated a flexible e!ongated molecule with dimensions of 151×59×43 Å. The quaternary structure of the C5b-7 complex bound toists of a leaflet and a long flexible stalk, and the dimer has two leaflets linked through a supercoiled stalk. Membrane binding is mediated by the stalk part of the complexes.
Individuals with inherited deficiencies of the terminal components of the complement system frequently suffer from recurrent systemic infections caused by Neisseria meningitidis or Neisseria gonorrhoeae, including meningococcal meningitis, meningococcemia, and disseminated gonococcal infection. Deficiencies in terminal complement components, including the complement C7, are uncommon and associated with an increased risk of recurrent systemic neisserial infection. A total of 22 molecular defects have been reported in the C7 gene with both complete (C7Q0) and subtotal (C7SD) C7 deficiencies.
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