Sequence analysis of a cDNA clone encoding the C-terminal end of human complement factor H.

Area of Science:

• Biochemistry
• Molecular Biology
• Immunology

Background:

• Factor H is a key regulatory protein in the complement system, crucial for immune response.
• Understanding Factor H's structure is vital for comprehending its function and potential therapeutic applications.

Purpose of the Study:

• To elucidate the structural organization of human factor H.
• To identify conserved domains within the factor H protein sequence.

Main Methods:

• Peptide sequencing was used to determine the amino acid sequence of factor H.
• Human liver cDNA libraries were screened using a synthesized oligonucleotide probe.
• Factor H-specific cDNA clones were selected and analyzed.

Main Results:

• A mixed sequence oligonucleotide probe was synthesized based on factor H peptide sequencing.
• Factor H-specific clones were isolated from human liver cDNA libraries.
• The largest isolated clone, R2a, encoded the C-terminal 657 amino acids of factor H.
• The derived amino acid sequence revealed 10 contiguous, internally homologous segments of approximately 60 amino acids each.
• Homologous sequences were identified in other complement and non-complement proteins.

Conclusions:

• The 10 homologous segments likely represent a conserved tertiary structure subunit within factor H.
• These findings provide insights into the modular organization of factor H and related proteins.
• The identified structural motifs may have implications for protein-protein interactions within the complement system.