Access the full text.
Sign up today, get DeepDyve free for 14 days.
C. Dellisanti, Yun Yao, J. Stroud, Zuo-Zhong Wang, Lin Chen (2007)
Crystal structure of the extracellular domain of nAChR α1 bound to α-bungarotoxin at 1.94 Å resolutionNature Neuroscience, 10
P. Purohit, A. Auerbach (2007)
Acetylcholine Receptor Gating: Movement in the α-Subunit Extracellular DomainThe Journal of General Physiology, 130
Analysis of the AChR Pre-M1 Linker
F. Vicente-Agulló, J. Rovira, S. Sala, F. Sala, C. Rodríguez-Ferrer, A. Campos-Caro, M. Criado, J. Ballesta (2001)
Multiple roles of the conserved key residue arginine 209 in neuronal nicotinic receptors.Biochemistry, 40 28
Archana Jha, David Cadugan, P. Purohit, A. Auerbach (2007)
Acetylcholine Receptor Gating at Extracellular Transmembrane Domain Interface: the Cys-Loop and M2–M3 LinkerThe Journal of General Physiology, 130
G. Cymes, C. Grosman, A. Auerbach (2002)
Structure of the transition state of gating in the acetylcholine receptor channel pore: a phi-value analysis.Biochemistry, 41 17
P. Celie, S. Rossum-fikkert, W. Dijk, K. Brejc, A. Smit, T. Sixma (2004)
Nicotine and Carbamylcholine Binding to Nicotinic Acetylcholine Receptors as Studied in AChBP Crystal StructuresNeuron, 41
A. Mitra, G. Cymes, A. Auerbach (2005)
Dynamics of the acetylcholine receptor pore at the gating transition state.Proceedings of the National Academy of Sciences of the United States of America, 102 42
T. Kash, Maria-Johanna Dizon, J. Trudell, N. Harrison (2004)
Charged Residues in the β2 Subunit Involved in GABAA Receptor Activation*Journal of Biological Chemistry, 279
A. Mitra, Timothy Bailey, A. Auerbach (2004)
Structural dynamics of the M4 transmembrane segment during acetylcholine receptor gating.Structure, 12 10
Xiangqun Hu, Li Zhang, R. Stewart, F. Weight (2003)
Arginine 222 in the Pre-transmembrane Domain 1 of 5-HT3A Receptors Links Agonist Binding to Channel Gating*Journal of Biological Chemistry, 278
Katjua Brejc, W. Dijk, R. Klaassen, M. Schuurmans, J. Oost, A. Smit, T. Sixma (2001)
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptorsNature, 411
Feng Qin, A. Auerbach, F. Sachs (1997)
Maximum likelihood estimation of aggregated Markov processesProceedings of the Royal Society of London. Series B: Biological Sciences, 264
K. Price, Katherine Millen, S. Lummis (2007)
Transducing Agonist Binding to Channel Gating Involves Different Interactions in 5-HT3 and GABAC Receptors*Journal of Biological Chemistry, 282
S. Chakrapani, Timothy Bailey, A. Auerbach (2003)
The Role of Loop 5 in Acetylcholine Receptor Channel GatingThe Journal of General Physiology, 122
Jinti Wang, H. Lester, D. Dougherty (2007)
Establishing an Ion Pair Interaction in the Homomeric ρ1 γ-Aminobutyric Acid Type A Receptor That Contributes to the Gating Pathway*Journal of Biological Chemistry, 282
Andersen served as editor
W. Lee, S. Sine (2005)
Principal pathway coupling agonist binding to channel gating in nicotinic receptorsNature, 438
P. Castaldo, P. Stefanoni, F. Miceli, G. Coppola, E. Giudice, G. Bellini, A. Pascotto, J. Trudell, N. Harrison, L. Annunziato, M. Taglialatela (2004)
A Novel Hyperekplexia-causing Mutation in the Pre-transmembrane Segment 1 of the Human Glycine Receptor α1 Subunit Reduces Membrane Expression and Impairs Gating by Agonists*Journal of Biological Chemistry, 279
S. Chakrapani, Timothy Bailey, A. Auerbach (2004)
Gating Dynamics of the Acetylcholine Receptor Extracellular DomainThe Journal of General Physiology, 123
A. Auerbach (2005)
Gating of acetylcholine receptor channels: brownian motion across a broad transition state.Proceedings of the National Academy of Sciences of the United States of America, 102 5
A. Auerbach (2007)
How to Turn the Reaction Coordinate into TimeThe Journal of General Physiology, 130
Xinan Xiu, Ariele Hanek, Jinti Wang, H. Lester, D. Dougherty (2005)
A Unified View of the Role of Electrostatic Interactions in Modulating the Gating of Cys Loop Receptors*Journal of Biological Chemistry, 280
S. Tamamizu, A. Todd, M. McNamee (1995)
Mutations in the M1 region of the nicotinic acetylcholine receptor alter the sensitivity to inhibition by quinacrineCellular and Molecular Neurobiology, 15
P. Purohit, A. Mitra, A. Auerbach (2007)
A stepwise mechanism for acetylcholine receptor channel gatingNature, 446
We would like thank Mary Merritt and Mary Teeling for technical assistance
J. Mercado, C. Czajkowski (2006)
Charged Residues in the α1 and β2 Pre-M1 Regions Involved in GABAA Receptor ActivationThe Journal of Neuroscience, 26
N. Unwin (2005)
Refined structure of the nicotinic acetylcholine receptor at 4A resolution.Journal of molecular biology, 346 4
A. Keramidas, ThomasL Kash, N. Harrison (2006)
The pre‐M1 segment of the α1 subunit is a transduction element in the activation of the GABAA receptorThe Journal of Physiology, 575
(2007)
Submitted: 17
Yu Zhou, J. Pearson, A. Auerbach (2005)
Phi-value analysis of a linear, sequential reaction mechanism: theory and application to ion channel gating.Biophysical journal, 89 6
David Cadugan, A. Auerbach (2007)
Conformational dynamics of the alphaM3 transmembrane helix during acetylcholine receptor channel gating.Biophysical journal, 93 3
Charged residues in the β10–M1 linker region (“pre-M1”) are important in the expression and function of neuromuscular acetylcholine receptors (AChRs). The perturbation of a salt bridge between pre-M1 residue R209 and loop 2 residue E45 has been proposed as being a principle event in the AChR gating conformational “wave.” We examined the effects of mutations to all five residues in pre-M1 (positions M207–P211) plus E45 in loop 2 in the mouse α 1 -subunit. M207, Q208, and P211 mutants caused small (approximately threefold) changes in the gating equilibrium constant (K eq ), but the changes for R209, L210, and E45 were larger. Of 19 different side chain substitutions at R209 on the wild-type background, only Q, K, and H generated functional channels, with the largest change in K eq (67-fold) from R209Q. Various R209 mutants were functional on different E45 backgrounds: H, Q, and K (E45A), H, A, N, and Q (E45R), and K, A, and N (E45L). Φ values for R209 (on the E45A background), L210, and E45 were 0.74, 0.35, and 0.80, respectively. Φ values for R209 on the wt and three other backgrounds could not be estimated because of scatter. The average coupling energy between 209/45 side chains (six different pairs) was only −0.33 kcal/mol (for both α subunits, combined). Pre-M1 residues are important for expression of functional channels and participate in gating, but the relatively modest changes in closed- vs. open-state energy caused mutations, the weak coupling energy between these residues and the functional activity of several unmatched-charge pairs are not consistent with the perturbation of a salt bridge between R209 and E45 playing the principle role in gating. Footnotes Abbreviations used in this paper: AChR, acetylcholine receptor; ECD, extracellular domain; REFER, rate-equilibrium free energy relationship; TMD, transmembrane domain. Submitted: 17 July 2007 Accepted: 8 November 2007
The Journal of General Physiology – Rockefeller University Press
Published: Dec 1, 2007
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.