Chapter 12 – Factor D

Factor D is a serine protease (SP) consisting of a single polypeptide of 228 amino acids. Unlike other SPs in the complement system, factor D circulates in the plasma as a mature but ‘resting-state’ form at a very low concentration and is produced mainly in adipocytes. The function of factor D is to cleave its unique substrate, factor B in Mg++-dependent complex with C3(H2O) or C3b, to generate the alternative pathway C3 convertases C3(H2O)Bb and C3bBb. Therefore, factor D is a key and rate-limiting component in the alternative pathway. Factor D participates in the amplification loop which contributes significantly to responses elicited by the complement classical and lectin pathways. Humans with factor D deficiency are rare and are phenotypically normal but encounter increased infection risk, particularly with Neisseria meningitidis.