title: Studies of binding of prekallikrein and Factor XI to high molecular weight kininogen and its light chain.
abstract: Prekallikrein and Factor XI have been reported to circulate as complexes with the coagulation cofactor high molecular weight (HMW)-kininogen. In this study we have shown that native HMW-kininogen possesses a strong binding site for prekallikrein and Factor XI with association constants of 3.4 x 10(7) M-1 and 4.2 x 10(8) M-1, respectively. The diminished binding of prekallikrein relative to Factor XI may, in part, account for the ability of kallikrein to leave the surface and interact with other molecules of Hageman factor and HMW-kininogen. Prekallikrein and Factor XI appear to compete for binding to HMW-kininogen, suggesting a single (or closely overlapping) binding site(s). The purified light chain derived from kinin-free HMW-kininogen is shown to compete with native MHW-kininogen for binding to Hageman factor substrates and direct binding of the isolated light chain to prekalikrein and Factor XI is demonstrated. This binding of the light chain to prekallikrein and Factor XI appears to be essential to the function of HMW-kininogen as a coagulation cofactor and further digestion of the light chain with excess kallikrein destroys its coagulant activity.
mesh_terms: D001665:Binding Sites; D005172:Factor XI / Q000378:metabolism*; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D007700:Kinetics; D007704:Kininogens / Q000378:metabolism*; D046911:Macromolecular Substances; D008970:Molecular Weight; D011288:Prekallikrein / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D007704:Kininogens; D046911:Macromolecular Substances; D005172:Factor XI; D011288:Prekallikrein; D007610:Kallikreins