Buldakova SL

References (2)

Title : Water-soluble LYNX1 residues important for interaction with muscle-type and\/or neuronal nicotinic receptors - Lyukmanova_2013_J.Biol.Chem_288_15888
Author(s) : Lyukmanova EN , Shulepko MA , Buldakova SL , Kasheverov IE , Shenkarev ZO , Reshetnikov RV , Filkin SY , Kudryavtsev DS , Ojomoko LO , Kryukova EV , Dolgikh DA , Kirpichnikov MP , Bregestovski PD , Tsetlin VI
Ref : Journal of Biological Chemistry , 288 :15888 , 2013
Abstract : Human LYNX1, belonging to the Ly6/neurotoxin family of three-finger proteins, is membrane-tethered with a glycosylphosphatidylinositol anchor and modulates the activity of nicotinic acetylcholine receptors (nAChR). Recent preparation of LYNX1 as an individual protein in the form of water-soluble domain lacking glycosylphosphatidylinositol anchor (ws-LYNX1; Lyukmanova, E. N., Shenkarev, Z. O., Shulepko, M. A., Mineev, K. S., D'Hoedt, D., Kasheverov, I. E., Filkin, S. Y., Krivolapova, A. P., Janickova, H., Dolezal, V., Dolgikh, D. A., Arseniev, A. S., Bertrand, D., Tsetlin, V. I., and Kirpichnikov, M. P. (2011) NMR structure and action on nicotinic acetylcholine receptors of water-soluble domain of human LYNX1. J. Biol. Chem. 286, 10618-10627) revealed the attachment at the agonist-binding site in the acetylcholine-binding protein (AChBP) and muscle nAChR but outside it, in the neuronal nAChRs. Here, we obtained a series of ws-LYNX1 mutants (T35A, P36A, T37A, R38A, K40A, Y54A, Y57A, K59A) and examined by radioligand analysis or patch clamp technique their interaction with the AChBP, Torpedo californica nAChR and chimeric receptor composed of the alpha7 nAChR extracellular ligand-binding domain and the transmembrane domain of alpha1 glycine receptor (alpha7-GlyR). Against AChBP, there was either no change in activity (T35A, T37A), slight decrease (K40A, K59A), and even enhancement for the rest mutants (most pronounced for P36A and R38A). With both receptors, many mutants lost inhibitory activity, but the increased inhibition was observed for P36A at alpha7-GlyR. Thus, there are subtype-specific and common ws-LYNX1 residues recognizing distinct targets. Because ws-LYNX1 was inactive against glycine receptor, its "non-classical" binding sites on alpha7 nAChR should be within the extracellular domain. Micromolar affinities and fast washout rates measured for ws-LYNX1 and its mutants are in contrast to nanomolar affinities and irreversibility of binding for alpha-bungarotoxin and similar snake alpha-neurotoxins also targeting alpha7 nAChR. This distinction may underlie their different actions, i.e. nAChRs modulation versus irreversible inhibition, for these two types of three-finger proteins.
ESTHER : Lyukmanova_2013_J.Biol.Chem_288_15888
PubMedSearch : Lyukmanova_2013_J.Biol.Chem_288_15888
PubMedID: 23585571

Title : Structural characteristics of ionotropic glutamate receptors as identified by channel blockade - Magazanik_2002_Neurosci.Behav.Physiol_32_173
Author(s) : Magazanik LG , Bol'shakov KV , Buldakova SL , Gmiro VE , Dorofeeva NA , Lukomskaya NY , Potap'eva NN , Samoilova MV , Tikhonov DB , Fedorova IM , Frolova EV
Ref : Neurosci Behav Physiol , 32 :173 , 2002
Abstract : The channels of four types of ionotropic glutamate receptor (NMDA receptors and Ca-permeable AMPA receptors of rat brain neurons, and cation-selective receptors from mollusk neurons and insect postsynaptic muscle membranes) and two subtypes of nicotinic cholinoreceptor (from frog neuromuscular junctions and cat sympathetic ganglia) were studied. The structural characteristics of channels determining their susceptibility to blockade by organic mono- and dications were identified. These studies used homologous series of adamantane and phenylcyclohexyl derivatives. These experiments showed that the receptors studied here could be divided into two groups. The first group included the AMPA receptor and the mollusk and insect receptors. These were characterized by the lack of effect on the part of monocations and a strong relationship between the activity of dications and the distance between nitrogen atoms. The second group included the NMDA receptor and both subtypes of the nicotinic cholinoreceptor (muscular and neuronal). Here, conversely, the activity of monocations and dications, regardless of their lengths, were essentially identical. A model for the binding sites of blockers in channels is proposed, which takes these observations into account.
ESTHER : Magazanik_2002_Neurosci.Behav.Physiol_32_173
PubMedSearch : Magazanik_2002_Neurosci.Behav.Physiol_32_173
PubMedID: 11942696