Loop2 Size Modification Reveals Significant Impacts on the Potency of α-Conotoxin TxID
α4/6-conotoxin TxID, which was identified from <i>Conus textile</i>, simultaneously blocks rat (r) α3β4 and rα6/α3β4 nicotinic acetylcholine receptors (nAChRs) with IC<sub>50</sub> values of 3.6 nM and 33.9 nM, respectively. In order to identify the effects of loop2 size on t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/21/5/286 |
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| author | Jianying Dong Panpan Zhang Junjie Xie Ting Xie Xiaopeng Zhu Dongting Zhangsun Jinpeng Yu Sulan Luo |
| author_facet | Jianying Dong Panpan Zhang Junjie Xie Ting Xie Xiaopeng Zhu Dongting Zhangsun Jinpeng Yu Sulan Luo |
| author_sort | Jianying Dong |
| collection | DOAJ |
| description | α4/6-conotoxin TxID, which was identified from <i>Conus textile</i>, simultaneously blocks rat (r) α3β4 and rα6/α3β4 nicotinic acetylcholine receptors (nAChRs) with IC<sub>50</sub> values of 3.6 nM and 33.9 nM, respectively. In order to identify the effects of loop2 size on the potency of TxID, alanine (Ala) insertion and truncation mutants were designed and synthesized in this study. An electrophysiological assay was used to evaluate the activity of TxID and its loop2-modified mutants. The results showed that the inhibition of 4/7-subfamily mutants [+9A]TxID, [+10A]TxID, [+14A]TxID, and all the 4/5-subfamily mutants against rα3β4 and rα6/α3β4 nAChRs decreased. Overall, ala-insertion or truncation of the 9th, 10th, and 11th amino acid results in a loss of inhibition and the truncation of loop2 has more obvious impacts on its functions. Our findings have strengthened the understanding of α-conotoxin, provided guidance for further modifications, and offered a perspective for future studies on the molecular mechanism of the interaction between α-conotoxins and nAChRs. |
| first_indexed | 2024-03-11T03:33:35Z |
| format | Article |
| id | doaj.art-8076fa7e53bf45ddaaf57abc1240ce68 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-11T03:33:35Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-8076fa7e53bf45ddaaf57abc1240ce682023-11-18T02:12:54ZengMDPI AGMarine Drugs1660-33972023-05-0121528610.3390/md21050286Loop2 Size Modification Reveals Significant Impacts on the Potency of α-Conotoxin TxIDJianying Dong0Panpan Zhang1Junjie Xie2Ting Xie3Xiaopeng Zhu4Dongting Zhangsun5Jinpeng Yu6Sulan Luo7School of Medicine, Guangxi University, Nanning 530004, ChinaSchool of Medicine, Guangxi University, Nanning 530004, ChinaSchool of Medicine, Guangxi University, Nanning 530004, ChinaSchool of Medicine, Guangxi University, Nanning 530004, ChinaSchool of Medicine, Guangxi University, Nanning 530004, ChinaKey Laboratory of Tropical Biological Resources, Ministry of Education, Key Laboratory for Marine Drugs of Haikou, Hainan University, Haikou 570228, ChinaSchool of Medicine, Guangxi University, Nanning 530004, ChinaSchool of Medicine, Guangxi University, Nanning 530004, Chinaα4/6-conotoxin TxID, which was identified from <i>Conus textile</i>, simultaneously blocks rat (r) α3β4 and rα6/α3β4 nicotinic acetylcholine receptors (nAChRs) with IC<sub>50</sub> values of 3.6 nM and 33.9 nM, respectively. In order to identify the effects of loop2 size on the potency of TxID, alanine (Ala) insertion and truncation mutants were designed and synthesized in this study. An electrophysiological assay was used to evaluate the activity of TxID and its loop2-modified mutants. The results showed that the inhibition of 4/7-subfamily mutants [+9A]TxID, [+10A]TxID, [+14A]TxID, and all the 4/5-subfamily mutants against rα3β4 and rα6/α3β4 nAChRs decreased. Overall, ala-insertion or truncation of the 9th, 10th, and 11th amino acid results in a loss of inhibition and the truncation of loop2 has more obvious impacts on its functions. Our findings have strengthened the understanding of α-conotoxin, provided guidance for further modifications, and offered a perspective for future studies on the molecular mechanism of the interaction between α-conotoxins and nAChRs.https://www.mdpi.com/1660-3397/21/5/286α-conotoxin TxIDα3β4 nAChRloop size modificationelectrophysiologyCD spectra |
| spellingShingle | Jianying Dong Panpan Zhang Junjie Xie Ting Xie Xiaopeng Zhu Dongting Zhangsun Jinpeng Yu Sulan Luo Loop2 Size Modification Reveals Significant Impacts on the Potency of α-Conotoxin TxID Marine Drugs α-conotoxin TxID α3β4 nAChR loop size modification electrophysiology CD spectra |
| title | Loop2 Size Modification Reveals Significant Impacts on the Potency of α-Conotoxin TxID |
| title_full | Loop2 Size Modification Reveals Significant Impacts on the Potency of α-Conotoxin TxID |
| title_fullStr | Loop2 Size Modification Reveals Significant Impacts on the Potency of α-Conotoxin TxID |
| title_full_unstemmed | Loop2 Size Modification Reveals Significant Impacts on the Potency of α-Conotoxin TxID |
| title_short | Loop2 Size Modification Reveals Significant Impacts on the Potency of α-Conotoxin TxID |
| title_sort | loop2 size modification reveals significant impacts on the potency of α conotoxin txid |
| topic | α-conotoxin TxID α3β4 nAChR loop size modification electrophysiology CD spectra |
| url | https://www.mdpi.com/1660-3397/21/5/286 |
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