High molecular weight kininogen interactions with the homologs prekallikrein and factor XI: importance to surface-induced coagulation.

ABSTRACT:

Background

In plasma, high molecular weight kininogen (HK) is either free or bound to prekallikrein (PK) or factor (F) XI (FXI). During contact activation, HK is thought to anchor PK and FXI to surfaces, facilitating their conversion to the proteases plasma kallikrein and FXIa. Mice lacking HK have normal hemostasis but are resistant to injury-induced arterial thrombosis.

Objectives

To identify amino acids on the HK-D6 domain involved in PK and FXI binding and study the importance of the HK-PK and HK-FXI interactions to coagulation.

Methods

Twenty-four HK variants with alanine replacements spanning residues 542-613 were tested in PK/FXI binding and activated partial thromboplastin time clotting assays. Surface-induced FXI and PK activation in plasma were studied in th

SUBMITTER: Mohammed BM 

PROVIDER: S-EPMC10841474 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature