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Basic and editing mechanisms underlying ion transport and regulation in NCX variants.
Cell Calcium ( IF 4.3 ) Pub Date : 2019-11-22 , DOI: 10.1016/j.ceca.2019.102131
Daniel Khananshvili 1
Affiliation  

Structure-dynamic analysis of archaeal NCX (NCX_Mj) provided new insights into the underlying mechanisms of ion selectivity, ion-coupled alternating access, ion occlusion, and transport catalysis. This knowledge is relevant, not only for prokaryotic and eukaryotic NCXs, but also for other families belonging to the superfamily of Ca2+/CA antiporters. In parallel with the ion transport mechanisms, the structure-dynamic determinants of regulatory CBD1 and CBD2 domains have been resolved according to which the Ca2+-induced allosteric signal is decoded at the two-domain interface and "secondarily" modified by a splicing segment at CBD2. The exon-dependent combinations within the splicing segment control the number of Ca2+ binding sites (from zero to three) at CBD2, as well as the Ca2+ binding affinity and Ca2+ off-rates at both CBDs. The exon-dependent combinations specifically rigidify the local segments at CBDs, yielding the Ca2+-dependent activation (through Ca2+ binding to CBD1) and Ca2+-dependent alleviation of Na+-induced inactivation (through Ca2+ binding with CBD2). The exon-dependent synergistic interactions between CBDs characteristically differ in NCX1 and NCX3, thereby underscoring the physiological relevance of structure-controlled shaping of ion-dependent regulation in tissue-specific NCX variants. How the ion-dependent regulatory modules operate in conjunction with other regulators (PIP2, palmitoylation, XIP, among the others) of NCX is an open question that remains to be determined.

中文翻译:

NCX变体中离子传输和调控的基础和编辑机制。

原型NCX(NCX_Mj)的结构动力学分析为离子选择性,离子耦合交替访问,离子闭塞和传输催化的潜在机制提供了新见解。该知识不仅与原核和真核NCX相关,而且与属于Ca2 + / CA反转运蛋白超家族的其他家族相关。与离子传输机制并行,调节性CBD1和CBD2域的结构动力学决定因素已得到解析,据此,Ca2 +诱导的变构信号在两个域界面处被解码,并被CBD2的剪接片段“第二次修饰” 。剪接片段中依赖外显子的组合控制着CBD2处Ca2 +结合位点的数量(从零到三个),以及两个CBD处的Ca2 +结合亲和力和Ca2 +脱速率。外显子依赖性组合特异性地硬化了CBD的局部片段,产生了Ca2 +依赖性激活(通过Ca2 +与CBD1的结合)和Ca2 +依赖性的Na +诱导的失活的缓解(通过Ca2 +与CBD2的结合)。CBD之间的外显子依赖性协同相互作用在NCX1和NCX3中具有特征性差异,从而突显了组织特异性NCX变体中离子依赖性调控的结构控制整形的生理相关性。依赖离子的调节模块如何与NCX的其他调节剂(PIP2,棕榈酰化,XIP等)结合使用是一个尚待确定的悬而未决的问题。产生Ca2 +依赖性激活(通过Ca2 +与CBD1结合)和Ca2 +依赖性缓解Na +诱导的失活(通过Ca2 +与CBD2结合)。CBD之间的外显子依赖性协同相互作用在NCX1和NCX3中具有特征性差异,从而突显了组织特异性NCX变体中离子依赖性调控的结构控制整形的生理相关性。依赖离子的调节模块如何与NCX的其他调节剂(PIP2,棕榈酰化,XIP等)结合使用是一个尚待确定的悬而未决的问题。产生Ca2 +依赖性激活(通过Ca2 +与CBD1结合)和Ca2 +依赖性缓解Na +诱导的失活(通过Ca2 +与CBD2结合)。CBD之间的外显子依赖性协同相互作用在NCX1和NCX3中具有特征性差异,从而突显了组织特异性NCX变体中离子依赖性调控的结构控制整形的生理相关性。依赖离子的调节模块如何与NCX的其他调节剂(PIP2,棕榈酰化,XIP等)结合使用是一个尚待确定的悬而未决的问题。从而强调了组织特异性NCX变体中离子依赖性调节的结构控制整形的生理相关性。依赖离子的调节模块如何与NCX的其他调节剂(PIP2,棕榈酰化,XIP等)结合使用是一个尚待确定的悬而未决的问题。从而强调了组织特异性NCX变体中离子依赖性调节的结构控制整形的生理相关性。依赖离子的调节模块如何与NCX的其他调节剂(PIP2,棕榈酰化,XIP等)结合使用是一个尚待确定的悬而未决的问题。
更新日期:2019-11-22
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