PMID: 9547372May 9, 1998Paper

Residues at the subunit interfaces of the nicotinic acetylcholine receptor that contribute to alpha-conotoxin M1 binding

Molecular Pharmacology
N SugiyamaP Taylor

Abstract

The two binding sites in the pentameric nicotinic acetylcholine receptor of subunit composition alpha2 beta gamma delta are formed by nonequivalent alpha-gamma and alpha-delta subunit interfaces, which produce site selectivity in the binding of agonists and antagonists. We show by sedimentation analysis that 125I-alpha-conotoxin M1 binds with high affinity to the alpha-delta subunit dimers, but not to alpha-gamma dimers, nor to alpha, gamma, and delta monomers, a finding consistent with alpha-conotoxin M1 selectivity for the alpha delta interface in the intact receptor measured by competition against alpha-bungarotoxin binding. We also extend previous identification of alpha-conotoxin M1 determinants in the gamma and delta subunits to the alpha subunit interface by mutagenesis of conserved residues in the alpha subunit. Most mutations of the alpha subunit affect affinity similarly at the two sites, but Tyr93Phe, Val188Lys, Tyr190Thr, Tyr198Thr, and Asp152Asn affect affinity in a site-selective manner. Mutant cycle analysis reveals only weak or no interactions between mutant alpha and non-alpha subunits, indicating that side chains of the alpha subunit do not interact with those of the gamma or delta subunits in stabilizing alph...Continue Reading

References

Sep 1, 1991·Biophysical Journal·G F TomaselliG Yellen
Jan 1, 1991·Annual Review of Pharmacology and Toxicology·J L GalziJ P Changeux
Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S E Pedersen, J B Cohen
Jan 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·T A Kunkel
Sep 1, 1994·Toxicon : Official Journal of the International Society on Toxinology·Y N UtkinV I Tsetlin
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

❮ Previous
Next ❯

Citations

Jun 29, 2000·Annual Review of Biochemistry·J M McIntoshB M Olivera
Jun 12, 2003·The Journal of Biological Chemistry·Hai-Long WangSteven M Sine
Jul 3, 1999·The Journal of Biological Chemistry·P A QuiramS M Sine
Mar 27, 2004·Molecular Pharmacology·J Michael McIntoshPaul Whiteaker
Mar 6, 2015·Molecular Pharmacology·Layla AzamJ Michael McIntosh
Jan 13, 2004·Physiological Reviews·Heinrich Terlau, Baldomero M Olivera
Apr 27, 2001·The Journal of Biological Chemistry·R V PapineniS E Pedersen
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Carole Fruchart-GaillardDenis Servent
Nov 25, 2000·The International Journal of Biochemistry & Cell Biology·H R Arias, M P Blanton
Jul 20, 2002·Biochemical and Biophysical Research Communications·Leonardo M CortezMirtha J Biscoglio de Jiménez Bonino
Sep 6, 2006·Toxicon : Official Journal of the International Society on Toxinology·Raymond S Norton, Baldomero M Olivera

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.