Matriptase is a type II transmembrane protease which is characterized by an N-terminal transmembrane and multiple extracellular domains, in addition to the conserved extracellular serine protease catalytic domain. The expression pattern of matriptase suggests that this protease may play broad roles in the biology of surface lining epithelial cells. In this study we report that alpha1-antitrypsin (AAT), an endogenous inhibitor of serine proteases, inhibits the catalytic domain of human recombinant matriptase in vitro. Co-incubation of alpha1-antitrypsin with matriptase (at a molar ratio 1:2) resulted in the formation of heat stable complexes, clearly seen in sodium dodecyl sulfate (SDS) electrophoresis and Western blots. AAT was found to be a slow, tight-binding inhibitor of the catalytic domain of matriptase with a second order reaction rate constant of 0.31 x10(3) M(-1)s(-1). Notably, the oxidised form of AAT, which lacks serine protease inhibitor activity, failed to generate matriptase complexes and to inhibit matriptase activity. Since matriptase is involved in a number of physiological processes including activation of epithelial sodium channels, our findings offer considerable new insights into new regulatory function of AAT in vivo.
The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Wallenberg Neuroscience Centre, Lund (0131000110), Chronic Inflammatory and Degenerative Diseases Research Unit (013242530), Emergency medicine/Medicine/Surgery (013240200), Faculty of Medicine (000022000)
- Cell and Molecular Biology
- serine proteases
- complex formation