Isolation and characterization of a partial cDNA clone for heparin cofactor II1

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Heparin cofactor II (HCII) is a plasma protein involved in regulating blood coagulation.
• Understanding the molecular basis of HCII's function is crucial for developing anticoagulant therapies.

Purpose of the Study:

• To clone and sequence the complementary DNA (cDNA) encoding the C-terminal region of human heparin cofactor II.
• To elucidate the structural basis for HCII's inhibitory activity against serine proteases.

Main Methods:

• Screening of a human fetal liver cDNA library using specific antibodies against HCII.
• Plaque purification and complete sequencing of the positive cDNA insert.
• Analysis of the deduced amino acid sequence, focusing on the protease cleavage site.

Main Results:

• A cDNA clone encoding the C-terminal 167 amino acid residues of HCII was isolated and sequenced.
• The P2 and P1 positions of the protease cleavage site were identified as proline and leucine, respectively.
• The determined coding sequence is identical to human leuserpin 2.

Conclusions:

• The identified amino acid sequence at the cleavage site provides a molecular explanation for HCII's inhibition of thrombin and chymotrypsin-like proteases.
• This study contributes to the understanding of HCII structure-function relationships.
• The findings support the identity between human heparin cofactor II and human leuserpin 2.