MOLECULAR MODELING AND MECHANISM OF ACTION OF HUMAN DECAY-ACCELERATING FACTOR

A model of the regulatory region of human decay accelerating factor (D AF) was built based on the known coordinates of a fragment of the stru cturally and functionally homologous serum protein, factor H. Accordin g to this model, the four short consensus repeats (SCRs) in DAF are ar ranged 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)over bar> and <(C3bBb)over bar>. 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 additi onal ligand binding sites. Based on this model in conjunction with seq uence homology to the Ba fragment of factor B, a mechanism of DAF's ac celerated convertase decay action is postulated.