Identification of Intrahelical Bifurcated H-Bonds as a New Type of Gate in K(+) Channels.
Identification of Intrahelical Bifurcated H-Bonds as a New Type of Gate in K(+) Channels.
复制标题
DOI：
10.1021/jacs.7b01158
复制
发表时间：
2017-06-07
影响因子：
15
通讯作者：
Schroeder I
中科院分区：
文献类型：
--
作者：
Rauh O;Urban M;Henkes LM;Winterstein T;Greiner T;Van Etten JL;Moroni A;Kast SM;Thiel G;Schroeder I
离子通道的门控基于开放和闭合状态之间的结构转变。为了揭示单个门的化学基础，我们在两个K+通道KcvS和KcvNTS之间进行了比较实验和计算分析。这些小病毒编码的K+通道蛋白，单体大小仅为82个氨基酸，在结构和功能方面类似于所有复杂K+通道的孔模块。尽管这两种蛋白质共享约90%的氨基酸序列同一性，但它们表现出不同的开放概率。KcvNTS为90%，KcvS为40%。单通道分析、突变研究和分子动力学模拟表明，KcvS中的一个长封闭态导致了开放概率的差异。这种状态在四聚体通道中通过瞬时的Ser介导的螺旋内氢键在结构上产生。在内部跨膜结构域中产生的扭结使芳香环从通道腔中的下游Phes摆动，这阻止了离子通量。膜蛋白中基于Ser或Thr的螺旋扭结的频繁发生表明类似的机制也可能发生在其他离子通道的门控中。
Gating of ion channels is based on structural transitions between open and closed states. To uncover the chemical basis of individual gates, we performed a comparative experimental and computational analysis between two K+ channels, KcvS and KcvNTS. These small viral encoded K+ channel proteins, with a monomer size of only 82 amino acids, resemble the pore module of all complex K+ channels in terms of structure and function. Even though both proteins share about 90% amino acid sequence identity, they exhibit different open probabilities with ca. 90% in KcvNTS and 40% in KcvS. Single channel analysis, mutational studies and molecular dynamics simulations show that the difference in open probability is caused by one long closed state in KcvS. This state is structurally created in the tetrameric channel by a transient, Ser mediated, intrahelical hydrogen bond. The resulting kink in the inner transmembrane domain swings the aromatic rings from downstream Phes in the cavity of the channel, which blocks ion flux. The frequent occurrence of Ser or Thr based helical kinks in membrane proteins suggests that a similar mechanism could also occur in the gating of other ion channels.
登录
查看更多内容
DOI：
10.1073/pnas.0711533105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Clayton, Gina M.;Altieri, Steve;Morais-Cabral, Joao H.
通讯作者：
Morais-Cabral, Joao H.
DOI：
10.1002/prot.340040208
发表时间：
1988-01-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
BRUNGER, AT;KARPLUS, M
通讯作者：
KARPLUS, M
DOI：
10.1042/bj20090095
发表时间：
2009-05-13
期刊：
The Biochemical journal
影响因子：
--
作者：
Gazzarrini S;Kang M;Abenavoli A;Romani G;Olivari C;Gaslini D;Ferrara G;van Etten JL;Kreim M;Kast SM;Thiel G;Moroni A
通讯作者：
Moroni A
影响因子：
4.4
作者：
FELLER, SE;ZHANG, YH;BROOKS, BR
通讯作者：
BROOKS, BR
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML