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Role of charged groups in factor XI/XIa activity
The Journal of Biological Chemistry
|October 10, 1982
Summary
Charged groups on factor XI are crucial for its function. Amino groups are essential for glass adsorption and activity, while amino and carboxyl groups are needed for activation by factor XII. All charged groups impact factor XIa
Area of Science:
- Biochemistry
- Hematology
- Molecular Biology
Background:
- Factor XI (FXI) and its activated form, FXIa, play a critical role in the intrinsic pathway of blood coagulation.
- Understanding the role of charged groups in FXI/FXIa function is essential for elucidating its coagulant activity and potential therapeutic targets.
Purpose of the Study:
- To investigate the specific roles of charged groups (amino, guanido, carboxyl) in the expression of factor XI coagulant activity.
- To determine how modification of these charged groups affects factor XI's adsorption, activation, and overall coagulant function.
Main Methods:
- Purified human blood coagulation factor XI/XIa was chemically modified to derivatize free amino, guanido (arginine), and carboxyl groups.
- Modified proteins were assessed for glass adsorption, susceptibility to cleavage by trypsin or factor XII-high molecular weight kininogen, and coagulant activity.
- Factor XIa activity was also evaluated after modification.
Main Results:
- Modification of amino groups significantly decreased glass adsorption, while arginine or carboxyl group modification had no effect.
- Trypsin cleaved factor XI regardless of modification, but factor XII-high molecular weight kininogen could only cleave arginine-modified factor XI.
- Amino and carboxyl group modifications abolished factor XI activity, while arginine modification retained 50%.
- Amino group modification prevented trypsin activation of FXI, but arginine and carboxyl modifications allowed 50% activation.
- Succinylation of FXIa amino groups destroyed all activity, whereas arginine and carboxyl modifications retained 50% activity.
Conclusions:
- Epsilon-amino groups are vital for factor XI adsorption to surfaces.
- Activation of factor XI by factor XII-high molecular weight kininogen necessitates the presence of free amino and carboxyl groups, but not guanido groups.
- Free amino, carboxyl, and guanido groups in factor XIa are all critical for its interaction with factor IX, highlighting their importance in the coagulation cascade.