title: Complete primary structure of human C4a anaphylatoxin.
abstract: C4a anaphylatoxin is derived from the fourth component (C4) of the blood complement system. The C4 alpha-chain is selectively cleaved between positions 77 and 78 by the protease C1s, a subcomponent of C1, generating the fragments C4a and C4b. Human C4a was isolated directly from fresh serum after C1 of the classical pathway of complement was activated by heat-aggregated gamma-globulin. The C4a anaphylatoxin is a cationic polypeptide of Mr = 9000 composed of 77 residues and devoid of histidine, tryptophan, and carbohydrate. The primary structure of human C4a was deduced from sequence analysis of two cyanogen bromide fragments and of peptides obtained after chymotryptic digestion of the COOH-terminal cyanogen bromide fragment. The proposed sequence is: (formula, see text) Manual alignment of the linear structures of human C3a, C4a, and C5a, based primarily on the location of two Cys-Cys sequences in each indicate a 30% homology between C3a and C4a and a 36% homology between C5a and C4a. It was concluded from the sequence comparison that C3a, C4a, and C5a are a family of bioactive factors derived from precursor molecules that share a common genetic origin. Although the human anaphylatoxins share a partial structural identity and express similar biological activities, these factors ae immunologically distinct molecules having no antigenic determinants in common as judged by radioimmunoassay.
mesh_terms: D000595:Amino Acid Sequence; D000706:Anaphylatoxins; D003181:Complement C4; D015934:Complement C4a; D003488:Cyanogen Bromide; D000939:Epitopes; D006801:Humans; D010446:Peptide Fragments / Q000032:analysis; D010455:Peptides; D011863:Radioimmunoassay
chemical_list: D000706:Anaphylatoxins; D003181:Complement C4; D000939:Epitopes; D010446:Peptide Fragments; D010455:Peptides; D015934:Complement C4a; D003488:Cyanogen Bromide