Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease.

The Journal of Biological Chemistry
Ce ZhangQingyu Wu

Abstract

Type II transmembrane serine proteases (TTSPs) are a group of enzymes participating in diverse biological processes. Some members of the TTSP family are implicated in viral infection. TMPRSS11A is a TTSP expressed on the surface of airway epithelial cells, which has been shown to cleave and activate spike proteins of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome coronaviruses (CoVs). In this study, we examined the mechanism underlying the activation cleavage of TMPRSS11A that converts the one-chain zymogen to a two-chain enzyme. By expression in human embryonic kidney 293, esophageal EC9706, and lung epithelial A549 and 16HBE cells, Western blotting, and site-directed mutagenesis, we found that the activation cleavage of human TMPRSS11A was mediated by autocatalysis. Moreover, we found that TMPRSS11A activation cleavage occurred before the protein reached the cell surface, as indicated by studies with trypsin digestion to remove cell surface proteins, treatment with cell organelle-disturbing agents to block intracellular protein trafficking, and analysis of a soluble form of TMPRSS11A without the transmembrane domain. We also showed that TMPRSS11A was able to cleave the SARS-CoV-2 spike p...Continue Reading

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Citations

Dec 11, 2020·The FEBS Journal·Shuo LiQingyu Wu
Oct 31, 2020·Biochemical Society Transactions·Ningzheng DongQingyu Wu
Oct 29, 2021·Molecular Systems Biology·Xiaonan LiuMarkku Varjosalo

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