Novel Three-Finger Neurotoxins from <i>Naja melanoleuca</i> Cobra Venom Interact with GABA<sub>A</sub> and Nicotinic Acetylcholine Receptors
Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABA<sub>A</sub> receptors (GABA<sub>A</sub>Rs) with different efficacy, an important role of the TFTs...
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MDPI AG
2021-02-01
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| Online Access: | https://www.mdpi.com/2072-6651/13/2/164 |
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| author | Lina Son Elena Kryukova Rustam Ziganshin Tatyana Andreeva Denis Kudryavtsev Igor Kasheverov Victor Tsetlin Yuri Utkin |
| author_facet | Lina Son Elena Kryukova Rustam Ziganshin Tatyana Andreeva Denis Kudryavtsev Igor Kasheverov Victor Tsetlin Yuri Utkin |
| author_sort | Lina Son |
| collection | DOAJ |
| description | Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABA<sub>A</sub> receptors (GABA<sub>A</sub>Rs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABA<sub>A</sub>R and here studied α-neurotoxins from African cobra <i>N. melanoleuca</i> venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known <i>N. melanoleuca</i> long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on <i>Torpedo</i><i>californica</i> and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABA<sub>A</sub>Rs, showed that all toxins interacted with the GABA<sub>A</sub>R much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABA<sub>A</sub>R was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABA<sub>A</sub>R. One of isolated toxins manifested different affinity to two binding sites on <i>Torpedo</i> nAChR. |
| first_indexed | 2024-03-09T00:40:42Z |
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| last_indexed | 2024-03-09T00:40:42Z |
| publishDate | 2021-02-01 |
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| series | Toxins |
| spelling | doaj.art-77039c6ad3904f05b320a5a553d206052023-12-11T17:50:53ZengMDPI AGToxins2072-66512021-02-0113216410.3390/toxins13020164Novel Three-Finger Neurotoxins from <i>Naja melanoleuca</i> Cobra Venom Interact with GABA<sub>A</sub> and Nicotinic Acetylcholine ReceptorsLina Son0Elena Kryukova1Rustam Ziganshin2Tatyana Andreeva3Denis Kudryavtsev4Igor Kasheverov5Victor Tsetlin6Yuri Utkin7Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaCobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABA<sub>A</sub> receptors (GABA<sub>A</sub>Rs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABA<sub>A</sub>R and here studied α-neurotoxins from African cobra <i>N. melanoleuca</i> venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known <i>N. melanoleuca</i> long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on <i>Torpedo</i><i>californica</i> and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABA<sub>A</sub>Rs, showed that all toxins interacted with the GABA<sub>A</sub>R much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABA<sub>A</sub>R was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABA<sub>A</sub>R. One of isolated toxins manifested different affinity to two binding sites on <i>Torpedo</i> nAChR.https://www.mdpi.com/2072-6651/13/2/164binding sitescobra venomGABA<sub>A</sub> receptorneurotoxinthree-finger toxinnicotinic acetylcholine receptor |
| spellingShingle | Lina Son Elena Kryukova Rustam Ziganshin Tatyana Andreeva Denis Kudryavtsev Igor Kasheverov Victor Tsetlin Yuri Utkin Novel Three-Finger Neurotoxins from <i>Naja melanoleuca</i> Cobra Venom Interact with GABA<sub>A</sub> and Nicotinic Acetylcholine Receptors Toxins binding sites cobra venom GABA<sub>A</sub> receptor neurotoxin three-finger toxin nicotinic acetylcholine receptor |
| title | Novel Three-Finger Neurotoxins from <i>Naja melanoleuca</i> Cobra Venom Interact with GABA<sub>A</sub> and Nicotinic Acetylcholine Receptors |
| title_full | Novel Three-Finger Neurotoxins from <i>Naja melanoleuca</i> Cobra Venom Interact with GABA<sub>A</sub> and Nicotinic Acetylcholine Receptors |
| title_fullStr | Novel Three-Finger Neurotoxins from <i>Naja melanoleuca</i> Cobra Venom Interact with GABA<sub>A</sub> and Nicotinic Acetylcholine Receptors |
| title_full_unstemmed | Novel Three-Finger Neurotoxins from <i>Naja melanoleuca</i> Cobra Venom Interact with GABA<sub>A</sub> and Nicotinic Acetylcholine Receptors |
| title_short | Novel Three-Finger Neurotoxins from <i>Naja melanoleuca</i> Cobra Venom Interact with GABA<sub>A</sub> and Nicotinic Acetylcholine Receptors |
| title_sort | novel three finger neurotoxins from i naja melanoleuca i cobra venom interact with gaba sub a sub and nicotinic acetylcholine receptors |
| topic | binding sites cobra venom GABA<sub>A</sub> receptor neurotoxin three-finger toxin nicotinic acetylcholine receptor |
| url | https://www.mdpi.com/2072-6651/13/2/164 |
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