Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 547, Issue -, Pages 82-88Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.01.107
Keywords
Insect-derived antimicrobial peptide CopA3; Caspase; Direct binding; Apoptosis; Inhibitor; Proteolytic cleavage
Categories
Funding
- Next-Generation BioGreen 21 Program [PJ01325602]
- Rural Development Administration, Republic of Korea
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Caspases are important in apoptotic processes, but over-activation can lead to diseases. CopA3 was found to directly bind to caspases and inhibit their activation, suggesting a potential therapeutic approach for diseases caused by uncontrolled apoptosis.
Caspases play essential roles in apoptotic processes, which is necessary for cellular homeostasis. However, over-activation of caspases and subsequent excessive apoptosis is considered a main cause of Parkinson's disease and liver diseases. Here, we found that the insect-derived peptide, CopA3, which has shown antiapoptotic effects in many apoptosis models, directly binds to caspases. The resulting complexes do not dissociate during denaturing polyacrylamide gel electrophoresis, as evidenced by a distinct shift in the migration of caspase reflecting an increase in their molecular weight. Surface plasmon resonance and experiment using cysteine-substituted mutants of CopA3 collectively revealed that binding of CopA3 to caspases is dependent on an internal cysteine residue. Notably, CopA3 binding significantly inhibited proteolytic activation of downstream caspases by upstream caspases. In summary, the demonstration that CopA3 directly binds to caspases and inhibits their activating cleavage suggests a possible therapeutic approach for treating human diseases resulting from uncontrolled apoptosis. (c) 2021 Elsevier Inc. All rights reserved.
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