The low pH stability of human coagulation factor XII (Hageman factor) is due to reversible conformational transitions.
Factor XII undergoes autoactivation when bound to negatively charged surfaces. To gain insight into the mechanism of factor XII autoactivation and stability at low pH, structural studies in the presence and absence of a soluble surface, dextran sulfate, at pH 5.3 and pH 8.3 were carried out. The circular dichroism data indicate that the secondary structure at pH 5.3 is only modestly different from that at pH 8.3. However, large changes in the secondary structure are found to occur when factor XII is exposed to pH 5.3 in the presence of surface. Changes in tertiary structure at low pH are also evident from the difference in tryptophan fluorescence and chemical reactivity of the histidine residues. Factor XII binds to the surface even at pH 5.3 though it is inactive at this pH. It is concluded that factor XII adopts a different conformation at pH 5.3 and causes it to interact differently with dextran sulfate. This results in an obstructed cleavage site that accounts for its stability at low pH.
Samuel
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Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595-1690.
Samuel
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E
Villanueva
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GB
D001665:Binding Sites; D002942:Circular Dichroism; D016264:Dextran Sulfate; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005174:Factor XII / Q000737:chemistry*; D005470:Fluorometry; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011487:Protein Conformation; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D013499:Surface Properties
D006639:Histidine; D005174:Factor XII; D016264:Dextran Sulfate