Ion-dependent structure, dynamics, and allosteric coupling in a non-selective cation channel.
Ion-dependent structure, dynamics, and allosteric coupling in a non-selective cation channel.
复制标题
DOI：
10.1038/s41467-021-26538-8
复制
发表时间：
2021-10-28
影响因子：
16.6
通讯作者：
Henzler-Wildman K
中科院分区：
文献类型：
--
作者：
Lewis A;Kurauskas V;Tonelli M;Henzler-Wildman K
选择性过滤器（SF）决定哪些离子能有效地通过离子通道孔。NaK是一种非选择性阳离子通道，以相同的效率传导Na+和K+。NaK的晶体结构显示为刚性的SF结构，但后来的固态核磁共振和MD模拟质疑了这一解释。在这里，我们使用溶液核磁共振来表征结合Na+和K+如何影响NaK SF结构和动力学。我们发现SF的胞外端在ps-ns时间尺度上是柔性的，而与结合的离子无关。在较慢的时间尺度上，我们观察到Na+和K+结合态之间的结构变化，伴随着Na+结构不均匀性的增加。我们还提供了直接证据，表明SF结构通过M2螺旋上的I88与孔连通。这些结果支持具有多种构象的动态SF参与非选择性传导。我们的数据还证明了非选择性阳离子通道中SF和孔衬螺旋之间的变构耦合，类似于之前在K+选择性通道中证明的变构耦合，支持了该模型的普遍性。NaK是一种细菌非选择性阳离子通道。本文作者利用溶液核磁共振表明，NaK中的选择性过滤器（SF）是动态的，具有Na+和K +结合态之间的结构差异。SF的构象与K +选择性通道类似，传递给孔衬螺旋。
The selectivity filter (SF) determines which ions are efficiently conducted through ion channel pores. NaK is a non-selective cation channel that conducts Na+ and K+ with equal efficiency. Crystal structures of NaK suggested a rigid SF structure, but later solid-state NMR and MD simulations questioned this interpretation. Here, we use solution NMR to characterize how bound Na+ vs. K+ affects NaK SF structure and dynamics. We find that the extracellular end of the SF is flexible on the ps-ns timescale regardless of bound ion. On a slower timescale, we observe a structural change between the Na+ and K+-bound states, accompanied by increased structural heterogeneity in Na+. We also show direct evidence that the SF structure is communicated to the pore via I88 on the M2 helix. These results support a dynamic SF with multiple conformations involved in non-selective conduction. Our data also demonstrate allosteric coupling between the SF and pore-lining helices in a non-selective cation channel that is analogous to the allosteric coupling previously demonstrated for K+-selective channels, supporting the generality of this model. NaK is a bacterial non-selective cation channel. Here, the authors use solution NMR to show that selectivity filter (SF) in NaK is dynamic, with structural differences between the Na+ and K + -bound states. The conformation of the SF is communicated to the pore-lining helices similarly as in the K + -selective channels.
登录
查看更多内容
影响因子：
7.7
作者：
Heer, Florian T.;Posson, David J.;Berneche, Simon
通讯作者：
Berneche, Simon
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
2.7
作者：
Chill, Jordan H.;Louis, John M.;Bax, Ad
通讯作者：
Bax, Ad
影响因子：
3.4
作者：
Jorgensen, Christian;Furini, Simone;Domene, Carmen
通讯作者：
Domene, Carmen