Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2
Tilapia piscidin (TP) 4 is an antimicrobial peptide derived from Nile tilapia (<i>Oreochromis niloticus</i>), which shows broad-spectrum antibacterial activity and excellent cancer-killing ability in vitro and in vivo. Like many other antimicrobial peptides, TP4 treatment causes mitochon...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/8/417 |
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| author | Bor-Chyuan Su Yi-Chung Liu Chen-Hung Ting Ping-Chiang Lyu Jyh-Yih Chen |
| author_facet | Bor-Chyuan Su Yi-Chung Liu Chen-Hung Ting Ping-Chiang Lyu Jyh-Yih Chen |
| author_sort | Bor-Chyuan Su |
| collection | DOAJ |
| description | Tilapia piscidin (TP) 4 is an antimicrobial peptide derived from Nile tilapia (<i>Oreochromis niloticus</i>), which shows broad-spectrum antibacterial activity and excellent cancer-killing ability in vitro and in vivo. Like many other antimicrobial peptides, TP4 treatment causes mitochondrial toxicity in cancer cells. However, the molecular mechanisms underlying TP4 targeting of mitochondria remain unclear. In this study, we used a pull-down assay on A549 cell lysates combined with LC-MS/MS to discover that TP4 targets adenine nucleotide translocator (ANT) 2, a protein essential for adenine nucleotide exchange across the inner membrane. We further showed that TP4 accumulates in mitochondria and colocalizes with ANT2. Moreover, molecular docking studies showed that the interaction requires Phe1, Ile2, His3, His4, Ser11, Lys14, His17, Arg21, Arg24 and Arg25 residues in TP4 and key residues within the cavity of ANT2. These findings suggest a mechanism by which TP4 may induce mitochondrial dysfunction to disrupt cellular energy metabolism. |
| first_indexed | 2024-03-10T17:44:48Z |
| format | Article |
| id | doaj.art-5e65c355ab2f4aeda16cea6f249d3831 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T17:44:48Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-5e65c355ab2f4aeda16cea6f249d38312023-11-20T09:35:02ZengMDPI AGMarine Drugs1660-33972020-08-0118841710.3390/md18080417Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2Bor-Chyuan Su0Yi-Chung Liu1Chen-Hung Ting2Ping-Chiang Lyu3Jyh-Yih Chen4Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, TaiwanInstitute of Population Sciences, National Health Research Institutes, 35 Keyan Rd., Zhunan, Miaoli County 350, TaiwanMarine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan 262, TaiwanInstitute of Bioinformatics and Structural Biology, National Tsing-Hua University, 101, Sec. 2, Kuang-Fu Rd., Hsinchu 300, TaiwanMarine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan 262, TaiwanTilapia piscidin (TP) 4 is an antimicrobial peptide derived from Nile tilapia (<i>Oreochromis niloticus</i>), which shows broad-spectrum antibacterial activity and excellent cancer-killing ability in vitro and in vivo. Like many other antimicrobial peptides, TP4 treatment causes mitochondrial toxicity in cancer cells. However, the molecular mechanisms underlying TP4 targeting of mitochondria remain unclear. In this study, we used a pull-down assay on A549 cell lysates combined with LC-MS/MS to discover that TP4 targets adenine nucleotide translocator (ANT) 2, a protein essential for adenine nucleotide exchange across the inner membrane. We further showed that TP4 accumulates in mitochondria and colocalizes with ANT2. Moreover, molecular docking studies showed that the interaction requires Phe1, Ile2, His3, His4, Ser11, Lys14, His17, Arg21, Arg24 and Arg25 residues in TP4 and key residues within the cavity of ANT2. These findings suggest a mechanism by which TP4 may induce mitochondrial dysfunction to disrupt cellular energy metabolism.https://www.mdpi.com/1660-3397/18/8/417antimicrobial peptide (AMP)tilapia piscidin 4 (TP4)adenine nucleotide translocator 2 (ANT2) |
| spellingShingle | Bor-Chyuan Su Yi-Chung Liu Chen-Hung Ting Ping-Chiang Lyu Jyh-Yih Chen Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2 Marine Drugs antimicrobial peptide (AMP) tilapia piscidin 4 (TP4) adenine nucleotide translocator 2 (ANT2) |
| title | Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2 |
| title_full | Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2 |
| title_fullStr | Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2 |
| title_full_unstemmed | Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2 |
| title_short | Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2 |
| title_sort | antimicrobial peptide tp4 targets mitochondrial adenine nucleotide translocator 2 |
| topic | antimicrobial peptide (AMP) tilapia piscidin 4 (TP4) adenine nucleotide translocator 2 (ANT2) |
| url | https://www.mdpi.com/1660-3397/18/8/417 |
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