Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal localization

• Published in: Biochemistry (Easton) 1986-07, Vol.25 (15), p.4292-4301
• Main Authors: BOCK, S. C, SKRIVER, K, SHOWS, T. B, MAGNUSSON, S, NIELSEN, E, THØGERSEN, H.-C, WIMAN, B, DONALDSON, V. H, EDDY, R. L, MARRINAN, J, RADZIEJEWSKA, E, HUBER, R
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Carbohydrates - analysis; Chromosome Mapping; Chromosomes, Human, 6-12 and X; Cloning, Molecular; Complement; Complement C1 Inactivator Proteins - genetics; Complement C1 Inactivator Proteins - isolation & purification; DNA - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes; Humans; Hybrid Cells - cytology; Models, Molecular; Molecular immunology; Nucleic Acid Hybridization; Polymorphism, Genetic; Protein Conformation
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00363a018

The primary structure of human C1 inhibitor was determined by peptide and DNA sequencing. The single-chain polypeptide moiety of the intact inhibitor is 478 residues (52,869 Da), accounting for only 51% of the apparent molecular mass of the circulating protein (104,000 Da). The positions of six glucosamine-based and five galactosamine-based oligosaccharides were determined. Another nine threonine residues are probably also glycosylated. Most of the carbohydrate prosthetic groups (probably 17) are located at the amino-terminal end (residues 1-120) of the protein and are particularly concentrated in a region where the tetrapeptide sequence Glx-Pro-Thr-Thr, and variants thereof, is repeated 7 times. No phosphate was detected in C1 inhibitor. Two disulfide bridges connect cysteine-101 to cysteine-406 and cysteine-108 to cysteine-183. Comparison of the amino acid and cDNA sequences indicates that secretion is mediated by a 22-residue signal peptide and that further proteolytic processing does not occur. C1 inhibitor is a member of the large serine protease inhibitor (serpin) gene family. The homology concerns residues 120 through the C-terminus. The sequence was compared with those of nine other serpins, and conserved and nonconserved regions correlated with elements in the tertiary structure of alpha 1-antitrypsin. The C1 inhibitor gene maps to chromosome 11, p11.2-q13. C1 inhibitor genes of patients from four hereditary angioneurotic edema kindreds do not have obvious deletions or rearrangements in the C1 inhibitor locus. A HgiAI DNA polymorphism, identified following the observation of sequence variants, will be useful as a linkage marker in studies of mutant C1 inhibitor genes.