Recombinant Human HMWK protein

HMWK (High Molecular Weight Kininogen) is a multifunctional plasma glycoprotein that plays a critical role in the intrinsic pathway of blood coagulation, inflammation, and the kallikrein-kinin system. As a key component of the contact activation system, it serves as a cofactor for the activation of factor XII (Hageman factor) and prekallikrein, ultimately leading to bradykinin release—a potent vasodilator and mediator of inflammatory responses. Structurally, HMWK consists of six domains (D1-D6) with distinct functional regions involved in binding to negatively charged surfaces, platelets, and endothelial cells.

Recombinant HMWK protein is engineered using biotechnological approaches to replicate the native protein's structure and function. This involves cloning the HMWK gene into expression vectors, followed by production in host systems such as bacterial, yeast, or mammalian cell cultures. Recombinant technology enables precise control over post-translational modifications critical for HMWK's biological activity, particularly glycosylation patterns in its heavy chain (D1-D3) and light chain (D5-D6).

The development of recombinant HMWK addresses challenges in studying and utilizing the native protein, which is difficult to isolate in pure form from plasma due to low abundance and complex interactions. It has become invaluable for research into coagulation disorders, vascular biology, and drug discovery—particularly for designing inhibitors targeting pathological bradykinin overproduction or contact system dysregulation. Additionally, recombinant HMWK serves as a standardized reagent in diagnostic assays and a potential therapeutic candidate for conditions involving kinin system imbalances. Its production underscores advancements in protein engineering to model complex plasma proteins for both basic science and clinical applications.