Amino acid sequence of human beta-factor XIIa

Area of Science:

• Biochemistry
• Molecular Biology
• Hematology

Background:

• Human factor XII is a key protein in the intrinsic pathway of the coagulation cascade.
• Understanding the structure and function of factor XII is crucial for elucidating blood clotting mechanisms.

Purpose of the Study:

• To determine the complete amino acid sequence of activated human beta-factor XIIa.
• To elucidate the structural characteristics and potential enzymatic function of beta-factor XIIa.

Main Methods:

• Activation of human factor XII with trypsin.
• Isolation of beta-factor XIIa using DEAE-Sephacel column chromatography.
• Peptide generation via enzymatic digestion (trypsin, chymotrypsin, S. aureus V8 protease) and chemical cleavage.
• Amino acid sequencing of peptides.

Main Results:

• The complete amino acid sequence of beta-factor XIIa was determined.
• Beta-factor XIIa is a glycoprotein with a heavy chain (243 residues) and a light chain (9 residues), linked by a disulfide bond.
• Carbohydrate moiety is attached to asparagine residue 61 of the heavy chain.
• The heavy chain sequence exhibits homology to other plasma serine proteases and pancreatic digestive enzymes.

Conclusions:

• Factor XII is the precursor of a typical serine protease.
• Beta-factor XIIa plays a role in the coagulation cascade.
• Structural homology suggests a conserved catalytic domain among serine proteases.