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Published VersionCC BY-NC-ND V4.0, Open Access
Journal article
Structural and functional characterisation of Tst2, a novel TRPV1 inhibitory peptide from the Australian sea anemone Telmatactis stephensoni
Biochimica et Biophysica Acta. Proteins and Proteomics, Vol.1872(1), pp.1-13
2024
PMID: 37640250
Abstract
Sea anemone venoms are complex mixtures of biologically active compounds, including disulfide-rich peptides, some of which have found applications as research tools, and others as therapeutic leads. Our recent transcriptomic and proteomic studies of the Australian sea anemone Telmatactis stephensoni identified a transcript for a peptide designated Tst2. Tst2 is a 38-residue peptide showing sequence similarity to peptide toxins known to interact with a range of ion channels (Na-V, TRPV1, K-V and Ca-V). Recombinant Tst2 (rTst2, which contains an additional Gly at the N-terminus) was produced by periplasmic expression in Escherichia coli, enabling the production of both unlabelled and uniformly C-13,N-15-labelled peptide for functional assays and structural studies. The LC-MS profile of the recombinant Tst2 showed a pure peak with molecular mass 6 Da less than that of the reduced form of the peptide, indicating the successful formation of three disulfide bonds from its six cysteine residues. The solution structure of rTst2 was determined using multidimensional NMR spectroscopy and revealed that rTst2 adopts an inhibitor cystine knot (ICK) structure. rTst2 was screened using various functional assays, including patch-clamp electrophysiological and cytotoxicity assays. rTst2 was inactive against voltage-gated sodium channels (Na-V) and the human voltage-gated proton (hHv1) channel. rTst2 also did not possess cytotoxic activity when assessed against Drosophila melanogaster flies. However, the recombinant peptide at 100 nM showed >50% inhibition of the transient receptor potential subfamily V member 1 (TRPV1) and slight (similar to 10%) inhibition of transient receptor potential subfamily A member 1 (TRPA1). Tst2 is thus a novel ICK inhibitor of the TRPV1 channel.
Details
- Title
- Structural and functional characterisation of Tst2, a novel TRPV1 inhibitory peptide from the Australian sea anemone Telmatactis stephensoni
- Authors
- Khaled A Elnahriry - Monash UniversityDorothy C C Wai - Monash UniversityLauren M Ashwood - Queensland University of TechnologyMuhammad Umair Naseem - University of DebrecenTibor G Szanto - University of DebrecenShaodong Guo - The University of QueenslandGyorgy Panyi - University of DebrecenPeter Prentis - Queensland University of TechnologyRaymond S Norton (Corresponding Author) - Monash University
- Publication details
- Biochimica et Biophysica Acta. Proteins and Proteomics, Vol.1872(1), pp.1-13
- Publisher
- Elsevier BV
- Date published
- 2024
- DOI
- 10.1016/j.bbapap.2023.140952
- ISSN
- 1570-9639
- PMID
- 37640250
- Copyright note
- © 2023 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
- Data Availability
- Data will be made available on request.
- Grant note
- KE acknowledges support from a Monash University scholarship (FPPS). This work was funded in part by the Hungarian National Research, Development and Innovation Office (K143071 to GP) and by a Stipendium Hungaricum Scholarship from the Tempus Public Foundation (to MUN).
- Organisation Unit
- School of Science, Technology and Engineering
- Language
- English
- Record Identifier
- 991054497902621
- Output Type
- Journal article
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