Solution Structures of the cis- and trans-Pro30 isomers of a novel 38-residue toxin from the venom of Hadronyche infensa sp. that contains a cystine-knot motif within its four disulfide bonds
Rosengren, K. Johan, Wilson, David, Daly, Norelle L., Alewood, Paul F., and Craik, David J. (2002) Solution Structures of the cis- and trans-Pro30 isomers of a novel 38-residue toxin from the venom of Hadronyche infensa sp. that contains a cystine-knot motif within its four disulfide bonds. Biochemistry, 41 (10). pp. 3294-3301.
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Abstract
The primary sequence and three-dimensional structure of a novel peptide toxin isolated from the Australian funnel-web spider Hadronyche infensa sp. is reported. ACTX-Hi:OB4219 contains 38 amino acids, including eight-cysteine residues that form four disulfide bonds. The connectivities of these disulfide bonds were previously unknown but have been unambiguously determined in this study. Three of these disulfide bonds are arranged in an inhibitor cystine-knot (ICK) motif, which is observed in a range of other disulfide-rich peptide toxins. The motif incorporates an embedded ring in the structure formed by two of the disulfides and their connecting backbone segments penetrated by a third disulfide bond. Using NMR spectroscopy, we determined that despite the isolation of a single native homologous product by RP-HPLC, ACTX-Hi:OB4219 possesses two equally populated conformers in solution. These two conformers were determined to arise from cis/trans isomerization of the bond preceding Pro30. Full assignment of the NMR spectra for both conformers allowed for the calculation of their structures, revealing the presence of a triple-stranded antiparallel β sheet consistent with the inhibitor cystine-knot (ICK) motif.
| Item ID: | 39020 |
|---|---|
| Item Type: | Article (Research - C1) |
| ISSN: | 1520-4995 |
| Funders: | Australian Research Council (ARC) |
| Date Deposited: | 03 Dec 2015 04:31 |
| FoR Codes: | 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060112 Structural Biology (incl Macromolecular Modelling) @ 100% |
| SEO Codes: | 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100% |
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