Alpha1-antitrypsin inhibits the activity of the matriptase catalytic domain in vitro.

American Journal of Respiratory Cell and Molecular Biology
Sabina JanciauskieneSadis Matalon

Abstract

Matriptase is a type II transmembrane protease that 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 AAT with matriptase (at a molar ratio 1:2) resulted in the formation of heat stable complexes, clearly seen in sodium dodecyl sulfate 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 x 10(3) M(-1)s(-1). Notably, the oxidized 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 physiologic processes, including activation of epithelial sodium channels, our findings offer considerable new insights into new regulatory function of AAT in vivo.

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Citations

Feb 22, 2012·Archivum Immunologiae Et Therapiae Experimentalis·David A BerginEmer P Reeves
Aug 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Danny JonigkSabina Janciauskiene
Jan 7, 2011·The Journal of Biological Chemistry·Estelle RousseletNabil G Seidah
Jul 12, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ahmed LazrakSadis Matalon
Jan 10, 2009·American Journal of Respiratory Cell and Molecular Biology·Ahmed LazrakSadis Matalon
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Dec 7, 2013·American Journal of Respiratory Cell and Molecular Biology·Ahmed LazrakSadis Matalon
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May 29, 2010·The Biochemical Journal·Toni M AntalisSarah Netzel-Arnett
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Feb 27, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Awen MenouBruno Crestani
Apr 1, 2017·American Journal of Respiratory Cell and Molecular Biology·Karina KrotovaMark L Brantly
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