Structural evidence that complement factor B constitutes a novel class of serine protease.

The 28,000-dalton COOH-terminal cyanogen bromide peptide of complement factor B was isolated disulfide bonded to a second polypeptide of Mr = 3,500. The amino acid sequence of the smaller peptide, CB2-3, and 51 of 55 NH2-terminal residues of the larger peptide, CB2-2, were determined on an automated sequenator. CB2-2 exhibited extensive homology in its primary structure to the known serine proteases and included the sequence, Ala-Ala-His-Cys, which is part of the active site of these enzymes. By contrast, CB2-3 demonstrated only limited sequence identity with the NH2 terminus of the serine proteases. Mild acid hydrolysis was employed to further cleave CB2-2 into fragments of Mr = 20,000 and 8,000. On analysis the 8,000-dalton peptide was observed to contain the active site serine sequence, Gly-Asp-Ser-Gly-Gly-Pro. The data, therefore, clearly document that factor B is also a serine protease, although its mechanism of activation differs from this class of proteolytic enzymes.