title: Modular toxin from the lynx spider Oxyopes takobius: Structure of spiderine domains in solution and membrane-mimicking environment.
abstract: We have recently demonstrated that a common phenomenon in evolution of spider venom composition is the emergence of so-called modular toxins consisting of two domains, each corresponding to a "usual" single-domain toxin. In this article, we describe the structure of two domains that build up a modular toxin named spiderine or OtTx1a from the venom of Oxyopes takobius. Both domains were investigated by solution NMR in water and detergent micelles used to mimic membrane environment. The N-terminal spiderine domain OtTx1a-AMP (41 amino acid residues) contains no cysteines. It is disordered in aqueous solution but in micelles, it assumes a stable amphiphilic structure consisting of two α-helices separated by a flexible linker. On the contrary, the C-terminal domain OtTx1a-ICK (59 residues) is a disulfide-rich polypeptide reticulated by five S-S bridges. It presents a stable structure in water and its core is the inhibitor cystine knot (ICK) or knottin motif that is common among single-domain neurotoxins. OtTx1a-ICK structure is the first knottin with five disulfide bridges and it represents a good reference for the whole oxytoxin family. The affinity of both domains to membranes was measured with NMR using titration by liposome suspensions. In agreement with biological tests, OtTx1a-AMP was found to show high membrane affinity explaining its potent antimicrobial properties.
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russia.|Moscow Institute of Physics and Technology (State University), 9 Institutskiy per, Dolgoprudny, Moscow Region, 141700, Russia.
authors.forename: Kirill D
authors.initials: KD
authors.lastname: Nadezhdin
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russia.|Moscow Institute of Physics and Technology (State University), 9 Institutskiy per, Dolgoprudny, Moscow Region, 141700, Russia.
authors.forename: Daria D
authors.initials: DD
authors.lastname: Romanovskaia
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russia.
authors.forename: Maria Y
authors.initials: MY
authors.lastname: Sachkova
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russia.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Oparin
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russia.
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Kovalchuk
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russia.
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Grishin
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russia.|Moscow Institute of Physics and Technology (State University), 9 Institutskiy per, Dolgoprudny, Moscow Region, 141700, Russia.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Arseniev
authors.affiliation: M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russia.
authors.forename: Alexander A
authors.identifier: 0000-0002-1359-0076
authors.initials: AA
authors.lastname: Vassilevski
mesh_terms: D000818:Animals; D060829:Arthropod Proteins / Q000737:chemistry*; D008567:Membranes, Artificial; D019906:Nuclear Magnetic Resonance, Biomolecular; D000072417:Protein Domains; D013111:Spider Venoms / Q000737:chemistry*; D013112:Spiders / Q000737:chemistry*
chemical_list: D060829:Arthropod Proteins; D008567:Membranes, Artificial; D013111:Spider Venoms
keywords: NMR; inhibitor cystine knot (ICK); knottin; membrane-active peptide; spider toxin; spider venom