HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 19, 15810-15815, May 11, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/19/15810    most recent M100788200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Utkin, Y. N. Articles by Tsetlin, V. I. Search for Related Content PubMed PubMed Citation Articles by Utkin, Y. N. Articles by Tsetlin, V. I. Social Bookmarking                      What's this?

"Weak Toxin" from Naja kaouthia Is a Nontoxic Antagonist of 7 and Muscle-type Nicotinic Acetylcholine Receptors^*

Yuri N. Utkin, Viktoriya V. Kukhtina, Elena V. Kryukova, Florence Chiodini^§, Daniel Bertrand^§, Christoph Methfessel^¶, and Victor I. Tsetlin

From the  Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya Str., V-437 Moscow GSP-7, 117997 Russia, the ^§ Department of Physiology, Centre Medical Universitaire, 1 Rue Michel Servet, 1211 Geneva 4, Switzerland, and ^¶ Central Research Biophysics, Bayer AG, D-51368 Leverkusen, Germany

A novel "weak toxin" (WTX) from Naja kaouthia snake venom competes with [¹²⁵I]-bungarotoxin for binding to the membrane-bound Torpedo californica acetylcholine receptor (AChR), with an IC₅₀ of ~2.2 µM. In this respect, it is ~300 times less potent than neurotoxin II from Naja oxiana and -cobratoxin from N. kaouthia, representing short-type and long-type -neurotoxins, respectively. WTX and -cobratoxin displaced [¹²⁵I]-bungarotoxin from the Escherichia coli-expressed fusion protein containing the rat 7 AChR N-terminal domain 1-208 preceded by glutathione S-transferase with IC₅₀ values of 4.3 and 9.1 µM, respectively, whereas for neurotoxin II the IC₅₀ value was >100 µM. Micromolar concentrations of WTX inhibited acetylcholine-activated currents in Xenopus oocyte-expressed rat muscle AChR and human and rat 7 AChRs, inhibiting the latter most efficiently (IC₅₀ of ~8.3 µM). Thus, a virtually nontoxic "three-fingered" protein WTX, although differing from -neurotoxins by an additional disulfide in the N-terminal loop, can be classified as a weak -neurotoxin. It differs from the short chain -neurotoxins, which potently block the muscle-type but not the 7 AChRs, and is closer to the long -neurotoxins, which have comparable potency against the above-mentioned AChR types.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				V. Avramopoulou, A. Mamalaki, and S. J. Tzartos Soluble, Oligomeric, and Ligand-binding Extracellular Domain of the Human {alpha}7 Acetylcholine Receptor Expressed in Yeast: REPLACEMENT OF THE HYDROPHOBIC CYSTEINE LOOP BY THE HYDROPHILIC LOOP OF THE ACh-BINDING PROTEIN ENHANCES PROTEIN SOLUBILITY J. Biol. Chem., September 10, 2004; 279(37): 38287 - 38293. [Abstract] [Full Text] [PDF]

				M. V. Skok, E. N. Kalashnik, L. N. Koval, V. I. Tsetlin, Y. N. Utkin, J.-P. Changeux, and R. Grailhe Functional Nicotinic Acetylcholine Receptors Are Expressed in B Lymphocyte-Derived Cell Lines Mol. Pharmacol., October 1, 2003; 64(4): 885 - 889. [Abstract] [Full Text] [PDF]

				S. Nirthanan, E. Charpantier, P. Gopalakrishnakone, M. C. E. Gwee, H.-E. Khoo, L.-S. Cheah, D. Bertrand, and R. M. Kini Candoxin, a Novel Toxin from Bungarus candidus, Is a Reversible Antagonist of Muscle (alpha beta gamma delta ) but a Poorly Reversible Antagonist of Neuronal alpha 7 Nicotinic Acetylcholine Receptors J. Biol. Chem., May 10, 2002; 277(20): 17811 - 17820. [Abstract] [Full Text] [PDF]