Molecular modeling and mechanism of action of human decay-accelerating factor.
A model of the regulatory region of human decay accelerating factor (DAF) was built based on the known coordinates of a fragment of the structurally and functionally homologous serum protein, factor H. According to this model, the four short consensus repeats (SCRs) in DAF are arranged in a helical fashion. A positively charged surface area on SCRs 2 and 3, two of the three repeating units essential for function, is postulated to be the primary recognition site for the C3 convertases C4b2a and C3bBb. This area encompasses a cavity on SCR 2, as well as part of the groove on the SCR 2-SCR 3 interface. Two additional surface depressions are centered around the C-terminal disulfide bridges of SCRs 3 and 4. These are likely to provide additional ligand binding sites. Based on this model in conjunction with sequence homology to the Ba fragment of factor B, a mechanism of DAF's accelerated convertase decay action is postulated.
Kuttner-Kondo
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Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106-4935, USA.
Medof
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ME
Brodbeck
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Shoham
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D000595:Amino Acid Sequence; D018958:CD55 Antigens / Q000737:chemistry* / Q000378:metabolism; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D018958:CD55 Antigens; D050577:Complement C3-C5 Convertases