The structure of human complement component C7 and the C5b-7 complex.
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 two-thirds 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. The secondary structural analysis, estimated by circular dichroism, suggested a high content of beta-sheet (38%) and beta-turns (24%). The tertiary structure, visualized by transmission electron microscopy, indicated a flexible elongated molecule with dimensions of 151 X 59 X 43 A. The quaternary structure of the C5b-7 complex bound to lipid vesicles was observed to be in the form of monomers or dimers. The monomer C5b-7 consists 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. 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.
DiScipio
R G
RG
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Chakravarti
D N
DN
Muller-Eberhard
H J
HJ
Fey
G H
GH
D000595:Amino Acid Sequence; D001483:Base Sequence; D002241:Carbohydrates / Q000032:analysis; D002942:Circular Dichroism; D003182:Complement C5; D003184:Complement C7 / Q000235:genetics; D003165:Complement System Proteins / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid
D002241:Carbohydrates; D003182:Complement C5; D003184:Complement C7; D046911:Macromolecular Substances; C037453:complement C5b-7 complex; D003165:Complement System Proteins