Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from <i>Conus geographus</i>
Conotoxins are disulfide-rich peptides found in the venom of cone snails. Due to their exquisite potency and high selectivity for a wide range of voltage and ligand gated ion channels they are attractive drug leads in neuropharmacology. Recently, cone snails were found to have the capability to rapi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/19/2/60 |
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| author | David A. Armstrong Ai-Hua Jin Nayara Braga Emidio Richard J. Lewis Paul F. Alewood K. Johan Rosengren |
| author_facet | David A. Armstrong Ai-Hua Jin Nayara Braga Emidio Richard J. Lewis Paul F. Alewood K. Johan Rosengren |
| author_sort | David A. Armstrong |
| collection | DOAJ |
| description | Conotoxins are disulfide-rich peptides found in the venom of cone snails. Due to their exquisite potency and high selectivity for a wide range of voltage and ligand gated ion channels they are attractive drug leads in neuropharmacology. Recently, cone snails were found to have the capability to rapidly switch between venom types with different proteome profiles in response to predatory or defensive stimuli. A novel conotoxin, GXIA (original name G117), belonging to the I<sub>3</sub>-subfamily was identified as the major component of the predatory venom of piscivorous <i>Conus geographus</i>. Using 2D solution NMR spectroscopy techniques, we resolved the 3D structure for GXIA, the first structure reported for the I<sub>3</sub>-subfamily and framework XI family. The 32 amino acid peptide is comprised of eight cysteine residues with the resultant disulfide connectivity forming an ICK+1 motif. With a triple stranded β-sheet, the GXIA backbone shows striking similarity to several tarantula toxins targeting the voltage sensor of voltage gated potassium and sodium channels. Supported by an amphipathic surface, the structural evidence suggests that GXIA is able to embed in the membrane and bind to the voltage sensor domain of a putative ion channel target. |
| first_indexed | 2024-03-09T03:39:27Z |
| format | Article |
| id | doaj.art-6c922537dfb2463ba969cc6accdf047f |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T03:39:27Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-6c922537dfb2463ba969cc6accdf047f2023-12-03T14:42:53ZengMDPI AGMarine Drugs1660-33972021-01-011926010.3390/md19020060Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from <i>Conus geographus</i>David A. Armstrong0Ai-Hua Jin1Nayara Braga Emidio2Richard J. Lewis3Paul F. Alewood4K. Johan Rosengren5School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaSchool of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, AustraliaConotoxins are disulfide-rich peptides found in the venom of cone snails. Due to their exquisite potency and high selectivity for a wide range of voltage and ligand gated ion channels they are attractive drug leads in neuropharmacology. Recently, cone snails were found to have the capability to rapidly switch between venom types with different proteome profiles in response to predatory or defensive stimuli. A novel conotoxin, GXIA (original name G117), belonging to the I<sub>3</sub>-subfamily was identified as the major component of the predatory venom of piscivorous <i>Conus geographus</i>. Using 2D solution NMR spectroscopy techniques, we resolved the 3D structure for GXIA, the first structure reported for the I<sub>3</sub>-subfamily and framework XI family. The 32 amino acid peptide is comprised of eight cysteine residues with the resultant disulfide connectivity forming an ICK+1 motif. With a triple stranded β-sheet, the GXIA backbone shows striking similarity to several tarantula toxins targeting the voltage sensor of voltage gated potassium and sodium channels. Supported by an amphipathic surface, the structural evidence suggests that GXIA is able to embed in the membrane and bind to the voltage sensor domain of a putative ion channel target.https://www.mdpi.com/1660-3397/19/2/60conotoxinvenomcone snailinhibitor cystine knot<i>Conus geographus</i>disulfide-rich |
| spellingShingle | David A. Armstrong Ai-Hua Jin Nayara Braga Emidio Richard J. Lewis Paul F. Alewood K. Johan Rosengren Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from <i>Conus geographus</i> Marine Drugs conotoxin venom cone snail inhibitor cystine knot <i>Conus geographus</i> disulfide-rich |
| title | Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from <i>Conus geographus</i> |
| title_full | Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from <i>Conus geographus</i> |
| title_fullStr | Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from <i>Conus geographus</i> |
| title_full_unstemmed | Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from <i>Conus geographus</i> |
| title_short | Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from <i>Conus geographus</i> |
| title_sort | chemical synthesis and nmr solution structure of conotoxin gxia from i conus geographus i |
| topic | conotoxin venom cone snail inhibitor cystine knot <i>Conus geographus</i> disulfide-rich |
| url | https://www.mdpi.com/1660-3397/19/2/60 |
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