Energetics of gating at the apo-acetylcholine receptor transmitter binding site.
Energetics of gating at the apo-acetylcholine receptor transmitter binding site.
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DOI：
10.1085/jgp.200910384
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Auerbach A
中科院分区：
文献类型：
--
作者：
Purohit P;Auerbach A
Acetylcholine receptor channels switch between conformations that have a low versus high affinity for the transmitter and conductance for ions (R↔R*; gating). The forward isomerization, which begins at the transmitter binding sites and propagates ∼50 Å to the narrow region of the pore, occurs by approximately the same sequence of molecular events with or without agonists present at the binding sites. To pinpoint the forces that govern the R versus R* agonist affinity ratio, we measured single-channel activation parameters for apo-receptors having combinations of mutations of 10 transmitter binding site residues in the α (Y93, G147, W149, G153, Y190, C192, and Y198), ε (W55 and P121), or δ (W57) subunit. Gating energy changes were largest for the tryptophan residues. The αW149 energy changes were coupled with those of the other aromatic amino acids. Mutating the aromatic residues to Phe reduces the R/R* equilibrium dissociation constant ratio, with αY190 and αW149 being the most sensitive positions. Most of the mutations eliminated long-lived spontaneous openings. The results provide a foundation for understanding how ligands trigger protein conformational change.
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影响因子：
3.4
作者：
GAO, J;CHOU, LW;AUERBACH, A
通讯作者：
AUERBACH, A
影响因子：
4.8
作者：
Bafna, Pallavi A.;Jha, Archana;Auerbach, Anthony
通讯作者：
Auerbach, Anthony
影响因子：
3.5
作者：
Chiara, DC;Middleton, RE;Cohen, JB
通讯作者：
Cohen, JB
影响因子：
5.5
作者：
Auerbach, Anthony
通讯作者：
Auerbach, Anthony
影响因子：
2.9
作者：
Grosman, C
通讯作者：
Grosman, C