PROSITE documentation PDOC51861Oxytoxin-type inhibitor cystine knot (ICK) domain profile
Spiders are widely acknowledged to produce potent and selective toxins. In addition to the conventional neurotoxins and cytotosins, venom of lynx spiders (genus Oxyopes) was found to contain two-domain modular toxins named spiderines: OspTx1a, 1b, 2a and 2b [1,2,3]. Spiderines consist of two distinct modules separated by a short linker. The N-terminal part (~40 residues) contains no cysteine residues, is highly cationic, forms amphipathic α-helical structures in a membrane-mimicking environment, and shows potent cytolytic effects on cells of various origins. The short linker resembles closely the processing quadruplet motif (PQM), which is known to indicate the processing cleavage site in precursors of spider toxins and separate the prosequence from the mature chain. The C-terminal part (~60 residues) is a disulfide rich domain reticulated by five S-S bridges) that is homologous to one-domain oxytoxins (OxyTx1 and OxyTx2) from Oxypes species. Oxytoxins are disulphide-rich polypeptides that contain five disulfide bridges and block L-, N- and P/Q-type voltage-sensitive calcium ion channels (VSCCs) [4].
The core of the oxytoxin-like domain is the inhibitor cystine knot (ICK) or knottin motif (see <PDB:2N86>). The domain is stabilized by five disulfides and 13 hydrogen bonds. Two antiparallel β-strands form a short β-sheet, and there are two β-turns in the N-terminal part of of the domain. C1-C5, C2-C6, and C4-C9 disulfides contribute to the ICK motif, whereas C7-C8 stabilizes the extended loop of the β-hairpin and C3-C10 staples the lengthy C-terminus of the domain to its core [3].
The profile we developed covers the entire oxytoxin-type ICK domain.
Last update:April 2018 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Vassilevski A.A. Sachkova M.Y. Ignatova A.A. Kozlov S.A. Feofanov A.V. Grishin E.V. |
| Title | Spider toxins comprising disulfide-rich and linear amphipathic domains: a new class of molecules identified in the lynx spider Oxyopes takobius. | |
| Source | FEBS. J. 280:6247-6261(2013). | |
| PubMed ID | 24118933 | |
| DOI | 10.1111/febs.12547 |
| 2 | Authors | Sachkova M.Y. Slavokhotova A.A. Grishin E.V. Vassilevski A.A. |
| Title | Genes and evolution of two-domain toxins from lynx spider venom. | |
| Source | FEBS Lett. 588:740-745(2014). | |
| PubMed ID | 24462682 | |
| DOI | 10.1016/j.febslet.2014.01.018 |
| 3 | Authors | Nadezhdin K.D. Romanovskaia D.D. Sachkova M.Y. Oparin P.B. Kovalchuk S.I. Grishin E.V. Arseniev A.S. Vassilevski A.A. |
| Title | Modular toxin from the lynx spider Oxyopes takobius: Structure of spiderine domains in solution and membrane-mimicking environment. | |
| Source | Protein Sci. 26:611-616(2017). | |
| PubMed ID | 27997708 | |
| DOI | 10.1002/pro.3101 |
| 4 | Authors | Villegas E. Adachi-Akahane S. Bosmans F. Tytgat J. Nakajima T. Corzo G. |
| Title | Biochemical characterization of cysteine-rich peptides from Oxyopes sp. venom that block calcium ion channels. | |
| Source | Toxicon 52:228-236(2008). | |
| PubMed ID | 18606178 | |
| DOI | 10.1016/j.toxicon.2008.05.019 |
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