A5004944388- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Cardiac electrophysiology and arrhythmias
- Lipid Membrane Structure and Behavior
- Neurobiology and Insect Physiology Research
- Neuroscience and Neural Engineering
- Electrochemical Analysis and Applications
- Molecular Sensors and Ion Detection
- Insect and Pesticide Research
- Nitric Oxide and Endothelin Effects
- Mass Spectrometry Techniques and Applications
- Electrochemical sensors and biosensors
- Hemoglobin structure and function
- Venomous Animal Envenomation and Studies
- Biotin and Related Studies
- Physiological and biochemical adaptations
- bioluminescence and chemiluminescence research
- Nuclear Physics and Applications
- Housing, Finance, and Neoliberalism
- Drug Transport and Resistance Mechanisms
- Public-Private Partnership Projects
Columbia University
2002-2024
University of Pennsylvania
2019-2023
Columbia University Irving Medical Center
2012
Institute of Molecular Biology and Biophysics
1985-2012
Royal College of Physicians
2012
University of Virginia
2002
Howard Hughes Medical Institute
2000
University of California, Los Angeles
2000
New York State Psychiatric Institute
1994
National Institute of Standards and Technology
1994
In order to understand the structural bases of ion conduction, selectivity, and gating in nicotinic acetylcholine receptor, mutagenesis covalent modification were combined identify amino acid residues that line channel. The side chains alternate residues—Ser248, Leu250, Ser252, Thr254—in M2, a membrane-spanning segment α subunit, are exposed closed Thus 248-254 probably forms β strand, gate is closer cytoplasmic end channel than any these residues. On opening, Leu251 also exposed. These...
Nicotinic acetylcholine receptors contain a readily reducible disulfide bond at the periphery of binding site.Following reduction this disulfide, site is susceptible to affinity labeling by electrophilic reagents with quaternary ammonium moieties.We reduced purified receptor from Torpedo californica electric tissue and alkylated it 4-(N-maleimido)benzyltri[SH]methylammonium iodide.The label was incorporated solely into subunit receptor.Isolated, labeled cleaved CNBr, fragments were separated...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular weight in detergent solution of acetylcholine receptor from Torpedo californicaJacqueline A. Reynolds and Arthur KarlinCite this: Biochemistry 1978, 17, 11, 2035–2038Publication Date (Print):May 30, 1978Publication History Published online1 May 2002Published inissue 30 1978https://doi.org/10.1021/bi00604a001RIGHTS & PERMISSIONSArticle Views229Altmetric-Citations314LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum full...
A conserved feature of all nicotinic receptors is the presence a readily reducible disulfide bond adjacent to acetylcholine binding site.Previously we showed that in intact receptor from Torpedo californica electric tissue reduction this followed by affinity alkylation with 4-(N-maleimido)ben~yItri[~H] methylammonium iodide specifically and uniquely labels CY subunit residues To identify half-cystinyl contributing site disulfide(s), have now reduced under mild conditions alkylated mixture...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrostatic potential of the acetylcholine binding sites in nicotinic receptor probed by reactions binding-site cysteines with charged methanethiosulfonatesDavid A. Stauffer and Arthur KarlinCite this: Biochemistry 1994, 33, 22, 6840–6849Publication Date (Print):June 7, 1994Publication History Published online1 May 2002Published inissue 7 June 1994https://pubs.acs.org/doi/10.1021/bi00188a013https://doi.org/10.1021/bi00188a013research-articleACS...
The receptor for acetylcholine in the subsynaptic membrane of electroplax Electrophorus electricus is a protein with disulfide bond vicinity active site. This can be reduced and reoxidized concomitant inhibition restoration response to other monoquaternary ammonium-depolarizing agents. Conversely, bisquaternary hexamethonium, normally competitive inhibitor, causes depolarization, activity decamethonium increased following reduction disulfide. alkylated by various maleimide derivatives then...
The structure of the NMDA receptor channel M2 segment was investigated by probing extracellular and cytoplasmic faces cysteine-substituted NR1-NR2C channels with charged sulfhydryl-specific reagents. pattern accessible positions suggests that forms a channel-lining loop originating ending on side channel, ascending limb in an alpha-helical descending extended structure. A functionally critical asparagine (N-site) is positioned at tip loop, cluster hydrophilic residues limb, adjacent to tip,...
There is evidence both for and against Na + - Cl − -dependent neurotransmitter transporters forming oligomers. We found that cross-linking the human dopamine transporter (DAT), which heterologously expressed in embryonic kidney 293 cells, either with copper phenanthroline (CuP) or bifunctional reagent bis-(2-methanethiosulfonatoethyl)amine hydrochloride (bis-EA) increased apparent molecular mass determined nonreducing SDS/PAGE from ≈85 to ≈195 kDa. After cross-linking, but not before,...
The cation-conducting channel of the nicotinic acetylcholine (ACh) receptor is lined by first (M1) and second (M2) membrane-spanning segments each its five subunits. Six consecutive residues, αS239 to αT244, in α subunit M1–M2 loop at intracellular end M2 were mutated cysteine. accessibility substituted cysteines probed with small, cationic, sulfhydryl-specific reagents added extracellularly intracellularly. In closed state channel, there a barrier these from either side between αG240 αT244....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIdentification of Acetylcholine Receptor Channel-Lining Residues in the M1 Segment .alpha.-SubunitMyles H. Akabas and Arthur KarlinCite this: Biochemistry 1995, 34, 39, 12496–12500Publication Date (Print):October 3, 1995Publication History Published online1 May 2002Published inissue 3 October 1995https://pubs.acs.org/doi/10.1021/bi00039a002https://doi.org/10.1021/bi00039a002research-articleACS PublicationsRequest reuse permissionsArticle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAffinity labeling of one two α-neurotoxin binding sites in acetylcholine receptor from Torpedo californicaVinayak N. Damle and Arthur KarlinCite this: Biochemistry 1978, 17, 11, 2039–2045Publication Date (Print):May 30, 1978Publication History Published online1 May 2002Published inissue 30 1978https://pubs.acs.org/doi/10.1021/bi00604a002https://doi.org/10.1021/bi00604a002research-articleACS PublicationsRequest reuse permissionsArticle...
Acetylcholine receptors transduce the binding of acetylcholine into a change in ionic permeability cell membranes. There are several types receptors, differentiated according to their specificities for activators (agonists) and inhibitors (antagonists) permeating ions (Grundfest 1974; Rang 1974). Distinct can coexist membrane (Kehoe 1972) or may predominate at different stages cellular differentiation (Patrick et al. 1972). The molecular bases phenomenological differences as yet unknown.
The receptor for acetylcholine was partially purified by affinity chromatography of an extract in Triton X-100 membrane fragments from electric tissue. assayed, after its reduction with dithiothreitol, reaction the affinity-alkylating agent, [methyl-(3)H]4-(N-maleimido)-benzyltrimethylammonium iodide. Alternative labeling procedures, one useful routine assay picomole quantities and other larger receptor, are described. specifically incorporated about 3 nmol label per mg protein. This...