+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Mutational analysis of the charge selectivity filter of the alpha7 nicotinic acetylcholine receptor

Mutational analysis of the charge selectivity filter of the alpha7 nicotinic acetylcholine receptor

Neuron 22(4): 831-843

In the alpha7 nicotinic acetylcholine receptors, we analyze the contribution of mutations E237A and V251T, together with the proline insertion P236', in the conversion of the charge selectivity from cationic to anionic. We show that the triple mutant exhibits spontaneous openings displaying anionic selectivity. Furthermore, at position 251, hydrophilic or even negatively charged residues are compatible with an anionic channel. In contrast, the additional proline yields an anionic channel only when inserted between positions 234 and 237; insertion before 234 yields a cationic channel and after 238 alters the receptor surface expression. The coiled 234-238 loop thus directly contributes to the charge selectivity filter of the alpha7 channel.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 011029907

Download citation: RISBibTeXText

PMID: 10230802

Related references

A7DB: a relational database for mutational, physiological and pharmacological data related to the alpha7 nicotinic acetylcholine receptor. Bmc Neuroscience 6: 2-2, 2005

The role of charge in lipid selectivity for the nicotinic acetylcholine receptor. Biophysical Journal 64(3): 632-641, 1993

Octahydropyrrolo[3,4-c]pyrrole: a diamine scaffold for construction of either alpha4beta2 or alpha7-selective nicotinic acetylcholine receptor (nAChR) ligands. Substitutions that switch subtype selectivity. Journal of Medicinal Chemistry 52(14): 4126-4141, 2009

Serotonin antagonizes the human neuronal alpha7 nicotinic acetylcholine receptor and becomes an agonist after L248T alpha7 mutation. Neuroscience 110(1): 169-179, 2002

Proteomic analysis of an alpha7 nicotinic acetylcholine receptor interactome. Journal of Proteome Research 8(4): 1849-1858, 2009

Molecular basis of the charge selectivity of nicotinic acetylcholine receptor and related ligand-gated ion channels. Novartis Foundation Symposium 225: 215-24; Discussion 224-30, 1999

Mutation analysis of the alpha7 nicotinic acetylcholine receptor gene and its partial duplication in schizophrenia patients. American Journal of Human Genetics 65(4): A271, 1999

Channel opening motion of alpha7 nicotinic acetylcholine receptor as suggested by normal mode analysis. Journal of Molecular Biology 355(2): 310-324, 2006

Association analysis of the partially duplicated alpha7 nicotinic acetylcholine receptor genetic variant and Alzheimer's disease. Dementia and Geriatric Cognitive Disorders 12(5): 301-304, 2001

Rigid nicotine analogs provide selectivity for alpha7 subunit-containing neuronal nicotinic acetylcholine receptors. Drug & Alcohol Dependence 60(Suppl 1): S80-S81, 1 December, 2000

Analysis of the involvement of the 2 bp deletion polymorphism of the alpha7 nicotinic acetylcholine receptor gene in P50 sensory gating deficit associated to schizophrenia. American Journal of Human Genetics 67(4 Suppl. 2): 352, 2000

Use of acetylcholine binding protein in the search for novel alpha7 nicotinic receptor ligands. In silico docking, pharmacological screening, and X-ray analysis. Journal of Medicinal Chemistry 52(8): 2372-2383, 2009

Potentials of mean force for acetylcholine unbinding from the alpha7 nicotinic acetylcholine receptor ligand-binding domain. Journal of the American Chemical Society 128(9): 3019-3026, 2006

Repeated administration of alpha7 nicotinic acetylcholine receptor (nAChR) agonists, but not positive allosteric modulators, increases alpha7 nAChR levels in the brain. Journal of Neurochemistry 114(4): 1205-1216, 2010

Kinetic properties of alpha7 nicotinic acetylcholine receptor channels of rat hippocampal neurons activated by choline and acetylcholine. Journal of Physiology (Cambridge) 526P: 103P, 2000