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Intracellular autoactivation of TMPRSS11A, an airway epithelial transmembrane serine protease.
Zhang, Ce; Zhang, Yikai; Zhang, Shengnan; Wang, Zhiting; Sun, Shijin; Liu, Meng; Chen, Yue; Dong, Ningzheng; Wu, Qingyu.
  • Zhang C; Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
  • Zhang Y; Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
  • Zhang S; MOH Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China.
  • Wang Z; Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
  • Sun S; MOH Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China.
  • Liu M; Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
  • Chen Y; Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
  • Dong N; MOH Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China.
  • Wu Q; Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
J Biol Chem ; 295(36): 12686-12696, 2020 09 04.
Article in English | MEDLINE | ID: covidwho-1387615
Semantic information from SemMedBD (by NLM)
1. Serine Endopeptidases PART_OF integral to membrane
Subject
Serine Endopeptidases
Predicate
PART_OF
Object
integral to membrane
2. TMPRSS11A gene|TMPRSS11A STIMULATES M Protei
Subject
TMPRSS11A gene|TMPRSS11A
Predicate
STIMULATES
Object
M Protei
3. TMPRSS11A gene|TMPRSS11A PART_OF Homo sapiens
Subject
TMPRSS11A gene|TMPRSS11A
Predicate
PART_OF
Object
Homo sapiens
4. Cell Surface Proteins STIMULATES TMPRSS11A gene|TMPRSS11A
Subject
Cell Surface Proteins
Predicate
STIMULATES
Object
TMPRSS11A gene|TMPRSS11A
5. M Protei PART_OF C5203676
Subject
M Protei
Predicate
PART_OF
Object
C5203676
6. Extracellular LOCATION_OF zymogen activation
Subject
Extracellular
Predicate
LOCATION_OF
Object
zymogen activation
7. Serine Endopeptidases PART_OF integral to membrane
Subject
Serine Endopeptidases
Predicate
PART_OF
Object
integral to membrane
8. TMPRSS11A gene|TMPRSS11A STIMULATES M Protein, multiple myeloma
Subject
TMPRSS11A gene|TMPRSS11A
Predicate
STIMULATES
Object
M Protein, multiple myeloma
9. TMPRSS11A gene|TMPRSS11A PART_OF Homo sapiens
Subject
TMPRSS11A gene|TMPRSS11A
Predicate
PART_OF
Object
Homo sapiens
10. Cell Surface Proteins STIMULATES TMPRSS11A gene|TMPRSS11A
Subject
Cell Surface Proteins
Predicate
STIMULATES
Object
TMPRSS11A gene|TMPRSS11A
11. M Protein, multiple myeloma PART_OF 2019 novel coronavirus
Subject
M Protein, multiple myeloma
Predicate
PART_OF
Object
2019 novel coronavirus
12. Extracellular LOCATION_OF zymogen activation
Subject
Extracellular
Predicate
LOCATION_OF
Object
zymogen activation
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 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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Epithelial Cells / Serine Proteases / Proteolysis / Membrane Proteins Subject: Epithelial Cells / Serine Proteases / Proteolysis / Membrane Proteins Language: English Journal: J Biol Chem Year: 2020

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Epithelial Cells / Serine Proteases / Proteolysis / Membrane Proteins Subject: Epithelial Cells / Serine Proteases / Proteolysis / Membrane Proteins Language: English Journal: J Biol Chem Year: 2020
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