Related Experiment Videos
C2 and factor B: structure and genetics
Insights
Complement components C2 and factor B are serine proteases within the major histocompatibility complex. DNA analysis reveals greater variability at the C2 locus than previously detected by protein typing.
Area of Science:
- Immunogenetics
- Molecular Biology
- Biochemistry
Background:
- Complement components C2 and factor B are serine proteases encoded by loci in the human major histocompatibility complex on chromosome 6.
- These proteins share significant homology, particularly in their catalytic and non-catalytic domains.
Purpose of the Study:
- To investigate the genetic structure and polymorphism of complement components C2 and factor B.
- To compare the variability detected at the DNA level with protein-level typing.
Main Methods:
- Molecular mapping and DNA sequence analysis of the C2 and factor B genes.
- Analysis of protein variants by charge differences.
- Restriction fragment length polymorphism (RFLP) analysis of the C2 gene.
Main Results:
- The factor B gene is 6 kb with 18 exons; the C2 gene is 18 kb, with a 425 bp intergenic region.
- Both C2 and factor B exhibit polymorphism, with two common factor B alleles (F and S) identified.
- DNA polymorphisms subdivide the C2 allotype C2C, indicating greater C2 locus variability than previously observed.
Conclusions:
- The C2 and factor B genes possess distinct structural features and are located closely on chromosome 6.
- DNA-level analysis reveals a higher degree of polymorphism at the C2 locus than protein typing suggests.
- These findings enhance our understanding of complement system genetic diversity within the MHC.
Abstract:
Complement components C2 and factor B are novel types of serine protease that are encoded by single loci in the major histocompatibility complex on human chromosome 6. The two proteins share 39% homology, or 50% taking into account conservative amino acid replacements. The catalytic chains, C2a (509 residues) and Bb (505 residues) show homology in their C-terminal domains to the catalytic polypeptides of other serine proteases. The non-catalytic chains, C2b (223 residues) and Ba (234 residues) both contain three tandem repeats of approx. 60 amino acids each, which are homologous to the repeats in C4b-binding protein and factor H, and also the repeats in the non-complement protein beta 2-glycoprotein I. Molecular mapping and DNA sequence analysis has shown that the factor B gene is 6 kb in length and contains 18 exons, while the C2 gene is 18 kb in length; 425 bp separates the 3' end of the C2 gene from the 5' end of the factor B gene. C2 and factor B are polymorphic and structural variants have been detected at the protein level by differences in charge. The degree of polymorphism at the factor B locus has been defined by DNA sequence analysis of the two common alleles F and S. In addition restriction fragment length polymorphisms have been detected in the C2 gene. These DNA polymorphisms subdivide the common allelic variant of C2 (C2C) and reveal that there is much greater variability at the C2 locus than that detected by protein typing.