The Secondary Structure of Human Hageman Factor (Factor XII) and its Alteration by Activating Agents

Abstract

A B S T R A C T Hageman factor (factor XII) is activated by exposure to surfaces such as glass or by solutions of certain compounds, notably ellagic acid. Changes in the structure of Hageman factor accompanying activation have been examined in this study by circular dichroism spectroscopy. The spectrum of unactivated Hageman factor in aqueous solutions suggests that its conformation is mainly aperiodic. Various perturbants altered the conformation of Hageman factor in differing ways, demonstrating the sensitivity of Hageman factor to its environment.After activation of Hageman factor with solutions of ellagic acid, a negative trough appeared in the region of the circular dichroism spectrum commonly assigned to tyrosine residues, along with other minor changes in the peptide spectral region. Some of these changes are similar to changes that occurred upon partial neutralization of the basic residues at alkali pH. Activation of Hageman factor by adsorption to quartz surfaces (in an aqueous environment) also produced changes similar to those in the ellagic acid-activated Hageman factor, including the negative ellipticity in the tyrosine region.These observations suggest that the activation process may be related to a change in status of some of the basic amino acid residues, coupled with a specific change in the environment of some tyrosine residues. The importance of these changes during the activation process remains to be determined. The

Isolation and properties of an abnormal Hageman factor (Factor XII) molecule in a cross-reacting material-positive hageman trait plasma.

“…Each protein band appeared to be associated with HF antigen. These amino acid analysis and pl data are essentially similar to those in previous reports (16)(17)(18).…”

Purification of High Molecular Weight Kininogen and the Role of This Agent in Blood Coagulation

“…Purified clotting factors, antibodies against clotting factors and procoagulant assays of HF, PTA, and plasma prekallikrein were prepared or performed as described earlier (4,(20)(21)(22). One unit of the procoagulant activity was arbitrarily defined as that amount present in 1 ml of a standard pooled plasma.…”

The relationship of structure and function in human Hageman factor. The association of enzymatic and binding activities with separate regions of the molecule.

“…Until recently, however, information concerning the molecular structure of the protein has been sparse and sometimes conflicting (2)(3)(4)(5)(6). The confusion has been undoubtedly due, in part, to the multiple forms of the enzymatically active Hageman factor moiety that result from differing purification and manipulatory techniques used by various investigators.…”