Mapping the conformational wave of acetylcholine receptor channel gating

Nature ◽  
2000 ◽  
Vol 403 (6771) ◽  
pp. 773-776 ◽  
Author(s):  
Claudio Grosman ◽  
Ming Zhou ◽  
Anthony Auerbach
Keyword(s):  
Acetylcholine Receptor ◽  
Channel Gating ◽  
Acetylcholine Receptor Channel ◽  
Receptor Channel

scholarly journals The Role of Loop 5 in Acetylcholine Receptor Channel Gating

2003 ◽  
Vol 122 (5) ◽  
pp. 521-539 ◽  
Author(s):  
Sudha Chakrapani ◽  
Timothy D. Bailey ◽  
Anthony Auerbach
Keyword(s):  
Binding Site ◽  
Acetylcholine Receptor ◽  
Single Channel ◽  
Channel Gating ◽  
Α Subunit ◽  
Acetylcholine Binding Protein ◽  
Relationship Analysis ◽  
Subunit Interface ◽  
Acetylcholine Receptor Channel ◽  
Receptor Channel

Nicotinic acetylcholine receptor channel (AChR) gating is an organized sequence of molecular motions that couples a change in the affinity for ligands at the two transmitter binding sites with a change in the ionic conductance of the pore. Loop 5 (L5) is a nine-residue segment (mouse α-subunit 92–100) that links the β4 and β5 strands of the extracellular domain and that (in the α-subunit) contains binding segment A. Based on the structure of the acetylcholine binding protein, we speculate that in AChRs L5 projects from the transmitter binding site toward the membrane along a subunit interface. We used single-channel kinetics to quantify the effects of mutations to αD97 and other L5 residues with respect to agonist binding (to both open and closed AChRs), channel gating (for both unliganded and fully-liganded AChRs), and desensitization. Most αD97 mutations increase gating (up to 168-fold) but have little or no effect on ligand binding or desensitization. Rate-equilibrium free energy relationship analysis indicates that αD97 moves early in the gating reaction, in synchrony with the movement of the transmitter binding site (Φ = 0.93, which implies an open-like character at the transition state). αD97 mutations in the two α-subunits have unequal energetic consequences for gating, but their contributions are independent. We conclude that the key, underlying functional consequence of αD97 perturbations is to increase the unliganded gating equilibrium constant. L5 emerges as an important and early link in the AChR gating reaction which, in the absence of agonist, serves to increase the relative stability of the closed conformation of the protein.

A stepwise mechanism for acetylcholine receptor channel gating

Nature ◽  
2007 ◽  
Vol 446 (7138) ◽  
pp. 930-933 ◽  
Author(s):  
Prasad Purohit ◽  
Ananya Mitra ◽  
Anthony Auerbach
Keyword(s):  
Acetylcholine Receptor ◽  
Channel Gating ◽  
Stepwise Mechanism ◽  
Acetylcholine Receptor Channel ◽  
Receptor Channel

scholarly journals Energy and Structure of the M2 Helix in Acetylcholine Receptor-Channel Gating

2009 ◽  
Vol 96 (10) ◽  
pp. 4075-4084 ◽  
Author(s):  
Archana Jha ◽  
Prasad Purohit ◽  
Anthony Auerbach
Keyword(s):  
Acetylcholine Receptor ◽  
Channel Gating ◽  
Acetylcholine Receptor Channel ◽  
Receptor Channel
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