The insect peptide CopA3 blocks programmed cell death by directly binding caspases and inhibiting their proteolytic activation.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Antimicrobial Cationic Peptides/*pharmacology ; Caspases/*metabolism ; Insect Proteins/*pharmacology ; Neoplasms/*drug therapy; Amino Acid Sequence ; Apoptosis/drug effects ; Caspases/chemistry ; Cell Line, Tumor ; Humans ; Neoplasms/metabolism ; Neoplasms/pathology ; Proteolysis ; Surface Plasmon Resonance/methods
    • Abstract:
      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.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2021 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Apoptosis; Caspase; Direct binding; Inhibitor; Insect-derived antimicrobial peptide CopA3; Proteolytic cleavage
    • Accession Number:
      0 (Antimicrobial Cationic Peptides)
      0 (CopA3 peptide, Copris tripartitus)
      0 (Insect Proteins)
      EC 3.4.22.- (Caspases)
    • Publication Date:
      Date Created: 20210220 Date Completed: 20210831 Latest Revision: 20210831
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.bbrc.2021.01.107
    • Accession Number:
      33610044