Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels.
Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels.
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DOI：
10.1038/ncomms1466
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发表时间：
2011-08-30
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
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离子通道四聚体的分子决定因素是很好的特点，但那些参与异聚体通道组装不太清楚。天然通道的异聚体组成通常是精确控制的。来自视杆细胞的环核苷酸门控（CNG）通道表现出CNGA 1和CNGB 1亚基的3：1化学计量比，其调节通道在光转导中的专门作用。在这里，我们表明，使用电生理学，荧光，生物化学，和X射线晶体学，这种受控组装的机制是形成一个平行的3-螺旋卷曲螺旋结构域的羧基末端亮氨酸拉链区域的CNGA 1亚基，约束通道包含三个CNGA 1亚基，然后优先纳入一个单一的CNGB 1亚基。羧基末端亮氨酸拉链结构域的缺失放松了限制，并允许通道中有多个CNGB 1亚基。CNGA 1和CNGA 3亚基的平行3-螺旋卷曲螺旋结构域的X射线晶体结构相似，表明相似的机制控制着锥形CNG通道的化学计量。本文的在线版本（doi：10.1038/ncomms 1466）包含补充材料，授权用户可以使用。异聚体离子通道的组装机制知之甚少。使用一系列技术，Shuartet等人确定了视杆细胞环核苷酸门控通道呈现CNGA 1和CNGB 1亚基的3：1化学计量的机制。本文的在线版本（doi：10.1038/ncomms 1466）包含补充材料，授权用户可以使用。
Molecular determinants of ion channel tetramerization are well characterized, but those involved in heteromeric channel assembly are less clearly understood. The heteromeric composition of native channels is often precisely controlled. Cyclic nucleotide-gated (CNG) channels from rod photoreceptors exhibit a 3:1 stoichiometry of CNGA1 and CNGB1 subunits that tunes the channels for their specialized role in phototransduction. Here we show, using electrophysiology, fluorescence, biochemistry, and X-ray crystallography, that the mechanism for this controlled assembly is the formation of a parallel 3-helix coiled-coil domain of the carboxy-terminal leucine zipper region of CNGA1 subunits, constraining the channel to contain three CNGA1 subunits, followed by preferential incorporation of a single CNGB1 subunit. Deletion of the carboxy-terminal leucine zipper domain relaxed the constraint and permitted multiple CNGB1 subunits in the channel. The X-ray crystal structures of the parallel 3-helix coiled-coil domains of CNGA1 and CNGA3 subunits were similar, suggesting that a similar mechanism controls the stoichiometry of cone CNG channels. The online version of this article (doi:10.1038/ncomms1466) contains supplementary material, which is available to authorized users. The assembly mechanisms of heteromeric ion channels are poorly understood. Using a range of techniques, Shuartet al.determine the mechanism by which rod photoreceptor cyclic nucleotide-gated channels assume a 3:1 stoichiometry of CNGA1 and CNGB1 subunits. The online version of this article (doi:10.1038/ncomms1466) contains supplementary material, which is available to authorized users.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
16.2
作者：
Howard, Rebecca J.;Clark, Kimberly A.;Minor, Daniel L., Jr.
通讯作者：
Minor, Daniel L., Jr.
影响因子：
16.2
作者：
KORSCHEN, HG;ILLING, M;MOLDAY, RS
通讯作者：
MOLDAY, RS
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
56.9
作者：
Long, SB;Campbell, EB;MacKinnon, R
通讯作者：
MacKinnon, R