2MQU
Spatial structure of Hm-3, a membrane-active spider toxin affecting sodium channels
Summary for 2MQU
| Entry DOI | 10.2210/pdb2mqu/pdb |
| NMR Information | BMRB: 25050 |
| Descriptor | Neurotoxin Hm-3 (1 entity in total) |
| Functional Keywords | spider toxins, voltage-gated sodium channels, gating modifiers, inhibitor cystine knot, ick, channel activation, toxin |
| Biological source | Heriaeus melloteei (Crab spider) |
| Total number of polymer chains | 1 |
| Total formula weight | 3919.71 |
| Authors | Myshkin, M.Y.,Shenkarev, Z.O.,Paramonov, A.S.,Berkut, A.A.,Grishin, E.V.,Vassilevski, A.A. (deposition date: 2014-06-27, release date: 2014-11-05, Last modification date: 2024-10-30) |
| Primary citation | Berkut, A.A.,Peigneur, S.,Myshkin, M.Y.,Paramonov, A.S.,Lyukmanova, E.N.,Arseniev, A.S.,Grishin, E.V.,Tytgat, J.,Shenkarev, Z.O.,Vassilevski, A.A. Structure of membrane-active toxin from crab spider Heriaeus melloteei suggests parallel evolution of sodium channel gating modifiers in Araneomorphae and Mygalomorphae. J. Biol. Chem., 290:492-504, 2015 Cited by PubMed Abstract: We present a structural and functional study of a sodium channel activation inhibitor from crab spider venom. Hm-3 is an insecticidal peptide toxin consisting of 35 amino acid residues from the spider Heriaeus melloteei (Thomisidae). We produced Hm-3 recombinantly in Escherichia coli and determined its structure by NMR spectroscopy. Typical for spider toxins, Hm-3 was found to adopt the so-called "inhibitor cystine knot" or "knottin" fold stabilized by three disulfide bonds. Its molecule is amphiphilic with a hydrophobic ridge on the surface enriched in aromatic residues and surrounded by positive charges. Correspondingly, Hm-3 binds to both neutral and negatively charged lipid vesicles. Electrophysiological studies showed that at a concentration of 1 μm Hm-3 effectively inhibited a number of mammalian and insect sodium channels. Importantly, Hm-3 shifted the dependence of channel activation to more positive voltages. Moreover, the inhibition was voltage-dependent, and strong depolarizing prepulses attenuated Hm-3 activity. The toxin is therefore concluded to represent the first sodium channel gating modifier from an araneomorph spider and features a "membrane access" mechanism of action. Its amino acid sequence and position of the hydrophobic cluster are notably different from other known gating modifiers from spider venom, all of which are described from mygalomorph species. We hypothesize parallel evolution of inhibitor cystine knot toxins from Araneomorphae and Mygalomorphae suborders. PubMed: 25352595DOI: 10.1074/jbc.M114.595678 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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