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Molecular mechanisms of two novel and selective TRPV1 channel activators.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2024 Aug; Vol. 275 (Pt 1), pp. 133658. Date of Electronic Publication: 2024 Jul 03. - Publication Year :
- 2024
-
Abstract
- Venomous toxins hold immense value as tools in elucidating the intricate structure and underlying mechanisms of ion channels. In this article, we identified of two novel toxins, Hainantoxin-XXI (HNTX-XXI) and Hainantoxin-XXII (HNTX-XXII), derived from the venom of the Chinese spider Ornithoctonus hainana. HNTX-XXI, boasting a molecular weight of 6869.095 Da, comprises 64 amino acid residues and contains 8 cysteines. Meanwhile, HNTX-XXII, with a molecular weight of 8623.732 Da, comprises 77 amino acid residues and contains 12 cysteines. Remarkably, we discovered that both HNTX-XXI and HNTX-XXII possess the ability to activate TRPV1. They activated TRPV1 with EC <subscript>50</subscript> values of 3.6 ± 0.19 μM and 862 ± 56 nM, respectively. Furthermore, the current generated by the activation of TRPV1 by these toxins can be rapidly blocked by ruthenium red. Intriguingly, our analysis revealed that the interaction between HNTX-XXI and TRPV1 is mediated by three key amino acid residues: L465, V469, and D471. Similarly, the interaction between HNTX-XXII and TRPV1 is facilitated by four key amino acid residues: A657, F659, E600, and R601. These findings provide profound insights into the molecular basis of toxin-TRPV1 interactions and pave the way for future research exploring the therapeutic potential of these toxic peptides.<br />Competing Interests: Declaration of competing interest The authors affirm that they do not have any financial or personal conflicts of interest that may have potentially influenced the research presented in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 275
- Issue :
- Pt 1
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 38969044
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2024.133658