Identification of residues in the neuronal alpha7 acetylcholine receptor that confer selectivity for conotoxin ImI.

The Journal of Biological Chemistry
P A Quiram, S M Sine

Abstract

To identify residues in the neuronal alpha7 acetylcholine subunit that confer high affinity for the neuronal-specific toxin conotoxin ImI (CTx ImI), we constructed alpha7-alpha1 chimeras containing segments of the muscle alpha1 subunit inserted into equivalent positions of the neuronal alpha7 subunit. To achieve high expression in 293 human embryonic kidney cells and formation of homo-oligomers, we joined the extracellular domains of each chimera to the M1 junction of the 5-hydroxytryptamine-3 (5HT-3) subunit. Measurements of CTx ImI binding to the chimeric receptors reveal three pairs of residues in equivalent positions of the primary sequence that confer high affinity of CTx ImI for alpha7/5HT-3 over alpha1/5HT-3 homo-oligomers. Two of these pairs, alpha7Trp55/alpha1Arg55 and alpha7Ser59/alpha1Gln59, are within one of the four loops that contribute to the traditional non-alpha subunit face of the muscle receptor binding site. The third pair, alpha7Thr77/alpha1Lys77, is not within previously described loops of either the alpha or non-alpha faces and may represent a new loop or an allosterically coupled loop. Exchanging these residues between alpha1 and alpha7 subunits exchanges the affinities of the binding sites for CTx ImI, ...Continue Reading

References

Sep 1, 1991·Biophysical Journal·G F TomaselliG Yellen
May 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·S J TzartosB M Conti-Tronconi
Aug 15, 1995·European Journal of Pharmacology·M GopalakrishnanJ P Sullivan
May 19, 1995·The Journal of Biological Chemistry·P J CorringerD Bertrand
Mar 1, 1994·The American Journal of Physiology·M E O'LearyM M White
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S M Sine
Jun 10, 1993·Nature

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Citations

Nov 25, 2000·The International Journal of Biochemistry & Cell Biology·H R Arias, M P Blanton
May 19, 2009·Acta Pharmacologica Sinica·Layla Azam, J Michael McIntosh
Sep 22, 1999·European Journal of Biochemistry·V Tsetlin
Apr 19, 2003·The Journal of Biological Chemistry·Fan GaoSteven M Sine
Jun 29, 2000·Annual Review of Biochemistry·J M McIntoshB M Olivera
Mar 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Chris UlensTitia K Sixma
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Nicolas Le NovèreJean-Pierre Changeux
May 27, 2014·Marine Drugs·Eline K M LebbeJan Tytgat
Jun 9, 2004·European Journal of Biochemistry·Emma L MillardDavid J Craik
Jun 9, 2004·European Journal of Biochemistry·Sébastien Dutertre, Richard J Lewis
Nov 18, 2005·Biochemical and Biophysical Research Communications·Seung-Wook ChiKyou-Hoon Han
Nov 17, 2017·Toxins·James T Daniel, Richard J Clark
Nov 18, 2015·Basic & Clinical Pharmacology & Toxicology·Azadeh ShahsavarThomas Balle
Dec 1, 2007·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Michael Ellison, Baldomero M Olivera
Feb 26, 2014·The Journal of Biological Chemistry·Eline K M LebbeJan Tytgat
Mar 13, 2012·Pharmacological Reviews·Richard J LewisMacDonald J Christie
Aug 25, 2005·Molecular Pharmacology·Diego RayesCecilia Bouzat
Oct 18, 2002·The Journal of Biological Chemistry·Michael EllisonBaldomero M Olivera
Jun 6, 1998·The Journal of Biological Chemistry·P A Quiram, S M Sine
Jul 11, 2012·Journal of Neurochemistry·Layla Azam, J Michael McIntosh
Feb 15, 2000·The Journal of Biological Chemistry·P A QuiramS M Sine
Jan 13, 2004·Physiological Reviews·Heinrich Terlau, Baldomero M Olivera
Oct 17, 2003·Neuroreport·Miguel VerbitskyA Belén Elgoyhen
Jul 3, 1999·The Journal of Biological Chemistry·P A QuiramS M Sine
Aug 31, 2013·Biomedit︠s︡inskai︠a︡ khimii︠a︡·A É FedosovB M Olivera
Dec 22, 2000·Journal of Molecular Biology·J P RogersR C Stevens

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