Plasticity of acetylcholine receptor gating motions via rate-energy relationships
Plasticity of acetylcholine receptor gating motions via rate-energy relationships
复制标题
DOI：
10.1529/biophysj.105.068783
复制
发表时间：
2005-11-01
影响因子：
3.4
通讯作者：
Licht, S
中科院分区：
文献类型：
--
作者：
Mitra, A;Tascione, R;Licht, S
像其他蛋白质构象变化一样，离子通道门控要求蛋白质达到高能过渡态结构。目前尚不清楚离子通道门控是发生在宽广的能量环境中，在该环境中许多可选的过渡态结构是可获得的，还是发生在仅有少数几种过渡态结构可能的狭窄能量环境中。为了解决这个问题，我们测量了双配体和非配体乙酰胆碱受体门控的速率平衡自由能关系(REFERS)如何随着门控平衡常数的变化而变化。REFER图的大斜率表示开放的过渡态，而小的斜率表示闭合的过渡态。由于REFERS和过渡态结构之间的这种关系，REFER斜率对突变诱导的能量扰动的敏感性允许估计门控下的能量景观的宽度。双配位参照斜率对能量微扰的相对较大的敏感性表明，双配位门控下的运动发生在一个宽广的、浅能量的场景中，在那里许多替代的过渡态结构是可以访问的。
Like other protein conformational changes, ion channel gating requires the protein to achieve a high-energy transition-state structure. It is not known whether ion channel gating takes place on a broad energy landscape on which many alternative transition state structures are accessible, or on a narrow energy landscape where only a few transition-state structures are possible. To address this question, we measured how rate-equilibrium free energy relationships (REFERs) for di-liganded and unliganded acetylcholine receptor gating vary as a function of the gating equilibrium constant. A large slope for the REFER plot indicates an openlike transition state, whereas a small slope indicates a closedlike transition state. Due to this relationship between REFERs and transition-state structure, the sensitivity of the REFER slope to mutation-induced energetic perturbations allows estimation of the breadth of the energy landscape underlying gating. The relatively large sensitivity of di-liganded REFER slopes to energetic perturbations suggests that the motions underlying di-liganded gating take place on a broad, shallow energy landscape where many alternative transition-state structures are accessible.