Interaction of alpha-conotoxin ImII and its analogs with nicotinic receptors and acetylcholine-binding proteins: additional binding sites on Torpedo receptor

Autor: Rustam H. Ziganshin, Daniel Bertrand, Titia K. Sixma, Victor I. Tsetlin, Alexander Fish, Prakash Rucktooa, Alexey V. Osipov, Igor E. Kasheverov, Alexey Yu. Khruschov, Maxim N. Zhmak, August B. Smit, Dieter D’hoedt
Přispěvatelé: Molecular and Cellular Neurobiology, Neuroscience Campus Amsterdam - Addictive Behavior
Jazyk: angličtina
Rok vydání: 2009
Předmět:
alpha7 Nicotinic Acetylcholine Receptor
Carrier Proteins/metabolism
Receptors
Nicotinic
Torpedo
Biochemistry
law.invention
Radioligand Assay
Acetylcholine binding
Xenopus laevis
law
Iodine Isotopes
Aplysia
Receptor
Conotoxins/chemistry/metabolism
Acetylcholine/pharmacology
Serine Endopeptidases
musculoskeletal system
Radioligand Assay/methods
Surface Plasmon Resonance/methods
Nicotinic acetylcholine receptor
Nicotinic agonist
Acetylcholine
medicine.drug
Stereochemistry
Iodine Isotopes/metabolism
Molecular Sequence Data
Biology
Binding
Competitive
complex mixtures
Cellular and Molecular Neuroscience
Inhibitory Concentration 50
SDG 3 - Good Health and Well-being
medicine
Animals
Humans
Receptors
Nicotinic/genetics/metabolism
Amino Acid Sequence
Binding site
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization/methods
Acetylcholine receptor
Binding Sites
Bungarotoxins/metabolism
Dose-Response Relationship
Drug
Binding
Competitive/drug effects
Surface Plasmon Resonance
Bungarotoxins
ddc:616.8
Binding Sites/drug effects/physiology
nervous system
Torpedo/metabolism
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
Oocytes
sense organs
Carrier Proteins
Conotoxins
Zdroj: Journal of Neurochemistry, Vol. 111, No 4 (2009) pp. 934-44
Kasheverov, I E, Zhmak, M N, Fish, A, Rucktooa, P, Khruschov, A Y, Osipov, A V, Ziganshin, R H, D'Hoedt, D, Bertrand, D, Sixma, T K, Smit, A B & Tsetlin, V I 2009, ' Interaction of alpha-conotoxin ImII and its analogs with nicotinic receptors and acetylcholine-binding proteins: additional binding sites on Torpedo receptor ', Journal of Neurochemistry, vol. 111, pp. 934-944 . https://doi.org/10.1111/j.1471-4159.2009.06359.x
Journal of Neurochemistry, 111, 934-944. Wiley-Blackwell
ISSN: 0022-3042
DOI: 10.1111/j.1471-4159.2009.06359.x
Popis: alpha-Conotoxins interact with nicotinic acetylcholine receptors (nAChRs) and acetylcholine-binding proteins (AChBPs) at the sites for agonists/competitive antagonists. alpha-Conotoxins blocking muscle-type or alpha7 nAChRs compete with alpha-bungarotoxin. However, alpha-conotoxin ImII, a close homolog of the alpha7 nAChR-targeting alpha-conotoxin ImI, blocked alpha7 and muscle nAChRs without displacing alpha-bungarotoxin (Ellison et al. 2003, 2004), suggesting binding at a different site. We synthesized alpha-conotoxin ImII, its ribbon isomer (ImIIiso), 'mutant' ImII(W10Y) and found similar potencies in blocking human alpha7 and muscle nAChRs in Xenopus oocytes. Both isomers displaced [(125)I]-alpha-bungarotoxin from human alpha7 nAChRs in the cell line GH(4)C(1) (IC(50) 17 and 23 microM, respectively) and from Lymnaea stagnalis and Aplysia californica AChBPs (IC(50) 2.0-9.0 microM). According to SPR measurements, both isomers bound to immobilized AChBPs and competed with AChBP for immobilized alpha-bungarotoxin (K(d) and IC(50) 2.5-8.2 microM). On Torpedo nAChR, alpha-conotoxin [(125)I]-ImII(W10Y) revealed specific binding (K(d) 1.5-6.1 microM) and could be displaced by alpha-conotoxin ImII, ImIIiso and ImII(W10Y) with IC(50) 2.7, 2.2 and 3.1 microM, respectively. As alpha-cobratoxin and alpha-conotoxin ImI displaced [(125)I]-ImII(W10Y) only at higher concentrations (IC(50)> or = 90 microM), our results indicate that alpha-conotoxin ImII and its congeners have an additional binding site on Torpedo nAChR distinct from the site for agonists/competitive antagonists.
Databáze: OpenAIRE
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