Gating movement of acetylcholine receptor caught by plunge-freezing.
Gating movement of acetylcholine receptor caught by plunge-freezing.
复制标题
DOI：
10.1016/j.jmb.2012.07.010
复制
发表时间：
2012-10-05
影响因子：
5.6
通讯作者：
Fujiyoshi, Yoshinori
中科院分区：
文献类型：
--
作者：
Unwin, Nigel;Fujiyoshi, Yoshinori
烟碱乙酰胆碱（ACh）受体在被释放到突触间隙的ACh激活时瞬时转化为开放通道形式。我们在这里描述的构象变化的基础上，这一事件，确定由乙酰胆碱喷雾和冷冻捕获突触后膜的电子显微镜。乙酰胆碱与α亚基结合后，在配体结合结构域中引发协同重排，涉及β亚基胞外部分向外位移约1 - 10倍，与α螺旋的并列末端相互作用，形成狭窄的跨膜孔。β-亚基螺旋向外倾斜以适应这种位移，使孔衬螺旋的排列不稳定，孔衬螺旋在封闭通道中对称地向内弯曲以形成中心疏水门。孔衬螺旋的拉直和切向运动通过不对称地加宽孔并增加其在浇口区域中的极性来影响通道开口。αγ和δ亚基的孔衬螺旋，通过在交替的弯曲和直的构象之间弯曲，经历最大的运动。这种偶联的变构转变使结构从紧张（封闭）状态向更松弛（开放）状态转变。乙酰胆碱在结合位点的作用被传递到约50 nm处的门。用喷雾冷冻捕集电子显微镜分析了结构变化。胞外结构域中的一个小的重排将β亚基向外推。这破坏了膜螺旋的封闭通道结构。α-γ和δ亚基的孔衬螺旋的弯曲是导致α-γ通道打开的主要原因。
The nicotinic acetylcholine (ACh) receptor converts transiently to an open-channel form when activated by ACh released into the synaptic cleft. We describe here the conformational change underlying this event, determined by electron microscopy of ACh-sprayed and freeze-trapped postsynaptic membranes. ACh binding to the α subunits triggers a concerted rearrangement in the ligand-binding domain, involving an ~ 1‐Å outward displacement of the extracellular portion of the β subunit where it interacts with the juxtaposed ends of α-helices shaping the narrow membrane-spanning pore. The β-subunit helices tilt outward to accommodate this displacement, destabilising the arrangement of pore-lining helices, which in the closed channel bend inward symmetrically to form a central hydrophobic gate. Straightening and tangential motion of the pore-lining helices effect channel opening by widening the pore asymmetrically and increasing its polarity in the region of the gate. The pore-lining helices of the αγ and δ subunits, by flexing between alternative bent and straight conformations, undergo the greatest movements. This coupled allosteric transition shifts the structure from a tense (closed) state toward a more relaxed (open) state. ► Effect of acetylcholine at binding site is communicated to the gate ~50Å away. ► The structural change has been analysed by spray-freeze-trapping electron microscopy. ► A small rearrangement in the extracellular domain pushes the β subunit outward. ► This destabilises the closed-channel configuration of membrane helices. ► Channel opens mainly by flexure of pore-lining helices of the αγ and δ subunits.
登录
查看更多内容
影响因子：
4.8
作者：
Dellisanti, Cosma D.;Hanson, Sonya M.;Czajkowski, Cynthia
通讯作者：
Czajkowski, Cynthia
DOI：
10.1073/pnas.90.13.6285
发表时间：
1993-07-01
影响因子：
11.1
作者：
CZAJKOWSKI, C;KAUFMANN, C;KARLIN, A
通讯作者：
KARLIN, A
影响因子：
2
作者：
Beckstein, O;Sansom, MSP
通讯作者：
Sansom, MSP
影响因子：
3.8
作者：
COHEN, BN;LABARCA, C;LESTER, HA
通讯作者：
LESTER, HA
影响因子：
64.8
作者：
Hilf, Ricarda J. C.;Dutzler, Raimund
通讯作者：
Dutzler, Raimund