Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease
Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease
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TMPRSS11A（一种气道上皮跨膜丝氨酸蛋白酶）的细胞内自动激活
DOI：
10.1074/jbc.ra120.014525
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发表时间：
2020-07
影响因子：
4.8
通讯作者：
Qingyu Wu
中科院分区：
文献类型：
--
作者：
Ce Zhang;Yikai Zhang;Shengnan Zhang;Zhiting Wang;Shijin Sun;Meng Liu;Yue Chen;Ningzheng Dong;Qingyu Wu
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 protein. These results reveal an intracellular autocleavage mechanism in TMPRSS11A zymogen activation, which differs from the extracellular zymogen activation reported in other TTSPs. These findings provide new insights into the diverse mechanisms in regulating TTSP activation.
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DOI：
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发表时间：
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期刊：
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