Determinants of coupled transport and uncoupled current by the electrogenic SLC26 transporters.
Determinants of coupled transport and uncoupled current by the electrogenic SLC26 transporters.
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DOI：
10.1085/jgp.201010531
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Muallem S
中科院分区：
文献类型：
--
作者：
Ohana E;Shcheynikov N;Yang D;So I;Muallem S
阴离子转运蛋白SLC26家族的成员介导从卤化物到羧酸等多种分子的转运，并且可以作为偶联转运体或通道发挥作用。该家族的两个成员Slc26a3和Slc26a6的一个独特特征是，它们根据所转运的阴离子不同，既可以作为强制性偶联转运体，也可以像通道一样介导非偶联电流。为了确定控制这两种转运模式的潜在特征，我们对Slc26a6进行了计算机模拟建模，结果表明，尽管Slc26a6跨膜结构域与CLC转运体的序列同源性极低，但它们在结构上最有可能相似。对预测的Slc26a6结构进行研究发现了一个高度保守的谷氨酸（Glu⁻；Slc26a6(E357)），其预测的空间取向与CLC - ec1的E148相似，而E148决定了CLC - ec1的偶联或非偶联转运。这就提出了一个问题，即Slc26a6(E357)和Slc26a3(E367)中保守的Glu⁻是否在这些转运体的独特转运模式中起作用。改变Slc26a3和Slc26a6中Glu⁻的电荷会导致所有转运模式受到抑制。然而，最值得注意的是，中和Slc26a6(E357A)的电荷会消除所有形式的偶联转运，而不影响非偶联电流。Slc26a3(E367A)突变显著降低了偶联转运，并将剩余交换的化学计量比从2Cl⁻/1HCO₃⁻转变为1Cl⁻/1HCO₃⁻，同时完全不影响电流。这些发现表明，类似的结构基序可能决定这些转运体的多种功能模式。
Members of the SLC26 family of anion transporters mediate the transport of diverse molecules ranging from halides to carboxylic acids and can function as coupled transporters or as channels. A unique feature of the two members of the family, Slc26a3 and Slc26a6, is that they can function as both obligate coupled and mediate an uncoupled current, in a channel-like mode, depending on the transported anion. To identify potential features that control the two modes of transport, we performed in silico modeling of Slc26a6, which suggested that the closest potential fold similarity of the Slc26a6 transmembrane domains is to the CLC transporters, despite their minimal sequence identity. Examining the predicted Slc26a6 fold identified a highly conserved glutamate (Glu−; Slc26a6(E357)) with the predicted spatial orientation similar to that of the CLC-ec1 E148, which determines coupled or uncoupled transport by CLC-ec1. This raised the question of whether the conserved Glu− in Slc26a6(E357) and Slc26a3(E367) have a role in the unique transport modes by these transporters. Reversing the Glu− charge in Slc26a3 and Slc26a6 resulted in the inhibition of all modes of transport. However, most notably, neutralizing the charge in Slc26a6(E357A) eliminated all forms of coupled transport without affecting the uncoupled current. The Slc26a3(E367A) mutation markedly reduced the coupled transport and converted the stoichiometry of the residual exchange from 2Cl−/1HCO3− to 1Cl−/1HCO3−, while completely sparing the current. These findings suggest the possibility that similar structural motif may determine multiple functional modes of these transporters.
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影响因子：
3.8
作者：
Accardi, Alessio;Walden, Michael;Nguitragool, Wang;Jayaram, Hariharan;Williams, Carole;Miller, Christopher
通讯作者：
Miller, Christopher
DOI：
10.1085/jgp.69.3.363
发表时间：
1977-03
期刊：
The Journal of general physiology
影响因子：
--
作者：
Knauf PA;Fuhrmann GF;Rothstein S;Rothstein A
通讯作者：
Rothstein A
影响因子：
3
作者：
Almståhl, A;Wikström, M
通讯作者：
Wikström, M
影响因子：
56.9
作者：
Dutzler, R;Campbell, EB;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
2.1
作者：
Boron, WF
通讯作者：
Boron, WF