Formation and structure of human Hageman factor fragments.

Abstract

Autodigestion of activated Hageman factor (HFa) yields a 40,000-mol wt activated enzyme as well as Hageman factor fragment (HFf); HFf consists of two molecular weight species of 28,500 and 30,000. We have investigated the structure of these active fragments and demonstrate that upon reduction, each possesses a heavy chain of 28,000. The associated light chains were identified by subjecting iodinated proteins to two-dimensional slab gel electrophoresis in which the second dimension is run reduced. The 40,000-dalton enzyme has a light chain of 15,000, the 30,000-dalton form of HFf has a light chain of 2,000 and we have suggestive evidence of a light chain associated with the 28,500-dalton form of HFf (putative mol wt approximately 500). We also demonstrate that the 30,000-dalton form of HFf precedes the 28,500 form. These data indicate that digestion of native HF to form HFa precedes cleavages that fragment the molecule and diminish its molecular weight. The 28,500-dalton light chain of HFa becomes the heavy chain of each of the fragmentation products while cleavage at different points along the heavy chain of HFa determines which fragments will be produced. In contrast to autoactivation, kallikrein digestion of HFa yields primarily HFf; however, the 40,000-dalton enzyme may be seen when prekallikrein-deficient (Fletcher trait) plasma is activated.