Старков Владислав Геннадьевич


Младший научный сотрудник (Лаборатория молекулярной токсинологии)

Тел.: +7 (495) 336-65-22

Эл. почта: vladislavstarkov@mail.ru

Избранные публикации

  1. Kudryavtsev D.S., Shelukhina I.V., Son L.V., Ojomoko L.O., Kryukova E.V., Lyukmanova E.N., Zhmak M.N., Dolgikh D.A., Ivanov I.A., Kasheverov I.E., Starkov V.G., Ramerstorfer J., Sieghart W., Tsetlin V.I., Utkin Y.N. (2015). Neurotoxins from Snake Venoms and α-Conotoxin ImI Inhibit Functionally Active Ionotropic GABA Receptors. J. Biol. Chem. , [+]

    Ionotropic receptors of γ-aminobutyric acid (GABAAR) regulate neuronal inhibition and are targeted by benzodiazepines and general anesthetics. We show that a fluorescent derivative of α-cobratoxin (α-Ctx), belonging to the family of three-finger toxins (TFTs) from snake venoms, specifically stained the α1β3γ2 receptor; at 10 μM α-Ctx completely blocked GABA-induced currents in this receptor expressed in Xenopus oocytes (IC50 = 236 nM) and less potently inhibited α1β2γ2 ≈ α2β2γ2 > α5β2γ2 > α2β3γ2 and α1β3δ GABAARs. The α1β3γ2 receptor was also inhibited by some other TFTs: long α-neurotoxin Ls III and non-conventional toxin WTX. α-Conotoxin ImI displayed inhibitory activity as well. Electrophysiology experiments showed mixed competitive and non-competitive α-Ctx action. Fluorescent α-Ctx, however, could be displaced by muscimol indicating that most of the α-Ctx binding sites overlap with the orthosteric sites at the β/α subunit interface. Modeling and molecular dynamic studies indicated that α-Ctx or α-bungarotoxin seem to interact with GABAAR in a way similar to their interaction with the acetylcholine-binding protein or the ligand-binding domain of nicotinic receptors. This was supported by mutagenesis studies and experiments with α-conotoxin ImI and a chimeric Naja oxiana α-neurotoxin indicating that the major role in α-Ctx binding to GABAAR is played by the tip of its central loop II accomodating under loop C of the receptors.

    ID:1307
  2. Osipov A.V., Kasheverov I.E., Makarova Y.V., Starkov V.G., Vorontsova O.V., Ziganshin R.K., Andreeva T.V., Serebryakova M.V., Benoit A., Hogg R.C., Bertrand D., Tsetlin V.I., Utkin Y.N. (2008). Naturally occurring disulfide-bound dimers of three-fingered toxins: a paradigm for biological activity diversification. J. Biol. Chem. 283 (21), 14571–80 [+]

    Впервые обнаружены трех-петельные токсины нового структурного типа: соединенные дисульфидами димеры кобратоксина с цитотоксинами, а также гомодимер кобратоксина. Показано, что в результате димеризации кобратоксин приобретает способность взаимодействовать с еще одним типом никотинового холинорецептора. Такая пост-трансляционная модификация может рассматриваться как еще один путь диверсификации биологической активности трех-петельных токсинов.

    ID:105
  3. Ramazanova A.S., Zavada L.L., Starkov V.G., Kovyazina I.V., Subbotina T.F., Kostyukhina E.E., Dementieva I.N., Ovchinnikova T.V., Utkin Y.N. (2008). Heterodimeric neurotoxic phospholipases A2--the first proteins from venom of recently established species Vipera nikolskii: implication of venom composition in viper systematics. Toxicon 51 (4), 524–37 [+]

    For the first time the venom of recently established viper species Vipera nikolskii was fractionated and two heterodimeric phospholipases A(2) (HDP-1 and HDP-2) were isolated. Isolation of HDP-1 and HDP-2 is the first indication of the presence of two heterodimeric phospholipases A(2) in the venom of one viper species. When tested on the frog neuromuscular junction, isolated proteins affected neuromuscular transmission acting presynaptically. Using RP-HPLC, each heterodimer was separated into two monomeric subunits: basic phospholipase A(2) (HDP-1P and HDP-2P) and acidic component without enzymatic activity (HDP-In). The complete primary structures of subunits were deduced from corresponding sequences of cDNAs. The determined amino acid sequences were homologous to those of vipoxin from Vipera ammodytes and vaspin from Vipera aspis. Similar proteins were not found earlier in the well-studied venom of Vipera berus, the species from which V. nikolskii was recently separated. Our finding supports at the biochemical level the correctness of the establishment of V. nikolskii as an independent species. The finding of similar proteins (HDPs and vipoxin) in geographically remote species (V. nikolskii and V. ammodytes) corroborates the hypothesis about the pre-existence of genes encoding these proteins in all true viper species and their expression under certain conditions.

    ID:413