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

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Human C1 inhibitor is a crucial component of the complement system.
• Understanding its structure is vital for studying complement-mediated disorders like hereditary angioneurotic edema.

Purpose of the Study:

• To determine the primary structure of human C1 inhibitor.
• To characterize its glycosylation and disulfide bridge formation.
• To investigate its relationship with the serine protease inhibitor (serpin) gene family.

Main Methods:

• Peptide and DNA sequencing were employed to determine the primary structure.
• Oligosaccharide positions and glycosylation sites were identified.
• Amino acid and cDNA sequences were compared to known serpins.
• Gene mapping and DNA polymorphism analysis were performed.

Main Results:

• The polypeptide moiety of C1 inhibitor consists of 478 residues.
• Multiple glucosamine- and galactosamine-based oligosaccharides are attached, primarily at the amino-terminal end.
• Two disulfide bridges were identified (Cys101-Cys406 and Cys108-Cys183).
• C1 inhibitor belongs to the serpin gene family, with homology to other members.
• The C1 inhibitor gene is located on chromosome 11, and no major deletions were found in hereditary angioneurotic edema patients.

Conclusions:

• The complete primary structure and glycosylation pattern of human C1 inhibitor were established.
• C1 inhibitor's classification within the serpin family was confirmed.
• A DNA polymorphism was identified, useful for linkage studies in hereditary angioneurotic edema.