Tags

Type your tag names separated by a space and hit enter

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. 2015 Jan 02; 290(1):492-504.JB

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.

Authors+Show Affiliations

From the M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia, Moscow Institute of Physics and Technology (State University), 117303 Moscow, Russia, and.Toxicology and Pharmacology, University of Leuven, 3000 Leuven, Belgium.From the M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia, Moscow Institute of Physics and Technology (State University), 117303 Moscow, Russia, and.From the M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.From the M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.From the M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia, Moscow Institute of Physics and Technology (State University), 117303 Moscow, Russia, and.From the M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.Toxicology and Pharmacology, University of Leuven, 3000 Leuven, Belgium.From the M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.From the M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia, avas@ibch.ru.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25352595

Citation

Berkut, Antonina A., et al. "Structure of Membrane-active Toxin From Crab Spider Heriaeus Melloteei Suggests Parallel Evolution of Sodium Channel Gating Modifiers in Araneomorphae and Mygalomorphae." The Journal of Biological Chemistry, vol. 290, no. 1, 2015, pp. 492-504.
Berkut AA, Peigneur S, Myshkin MY, et al. 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. 2015;290(1):492-504.
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. (2015). Structure of membrane-active toxin from crab spider Heriaeus melloteei suggests parallel evolution of sodium channel gating modifiers in Araneomorphae and Mygalomorphae. The Journal of Biological Chemistry, 290(1), 492-504. https://doi.org/10.1074/jbc.M114.595678
Berkut AA, et al. 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. 2015 Jan 2;290(1):492-504. PubMed PMID: 25352595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structure of membrane-active toxin from crab spider Heriaeus melloteei suggests parallel evolution of sodium channel gating modifiers in Araneomorphae and Mygalomorphae. AU - Berkut,Antonina A, AU - Peigneur,Steve, AU - Myshkin,Mikhail Yu, AU - Paramonov,Alexander S, AU - Lyukmanova,Ekaterina N, AU - Arseniev,Alexander S, AU - Grishin,Eugene V, AU - Tytgat,Jan, AU - Shenkarev,Zakhar O, AU - Vassilevski,Alexander A, Y1 - 2014/10/28/ PY - 2014/10/30/entrez PY - 2014/10/30/pubmed PY - 2015/4/8/medline KW - Channel Activation KW - Electrophysiology KW - Gating Modifiers KW - Inhibitor Cystine Knot KW - Ion Channel KW - Neurotoxin KW - Nuclear Magnetic Resonance (NMR) KW - Sodium Channel KW - Spider Toxins KW - Toxin SP - 492 EP - 504 JF - The Journal of biological chemistry JO - J Biol Chem VL - 290 IS - 1 N2 - 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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/25352595/Structure_of_membrane_active_toxin_from_crab_spider_Heriaeus_melloteei_suggests_parallel_evolution_of_sodium_channel_gating_modifiers_in_Araneomorphae_and_Mygalomorphae_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)57946-5 DB - PRIME DP - Unbound Medicine ER -