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首页> 外文期刊>Biochemistry >The Role of Local Hydration and Hydrogen-Bonding Dynamics in Ion and Solute Release from Ion-Coupled Secondary Transporters
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The Role of Local Hydration and Hydrogen-Bonding Dynamics in Ion and Solute Release from Ion-Coupled Secondary Transporters

机译：局部水化和氢键动力学在离子和溶质从离子耦合的二级转运体释放中的作用

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Recent progress in crystallographic studies of sodium-coupled secondary transporters hasnrevealed striking similarities in the structural organization of ion and solute binding. Previous reportsnsuggested that the Na2 sodium binding site in the neurotransmitter sodium symporter (NSS) leucinentransporter (LeuT) is conserved across sodium/proton coupled secondary transporters of many distantlynrelated families. This site is implicated in the conformational dynamics controlled by the binding and releasenof both translocated solute and ion(s) through a mechanism that largely remains unknown. In this study, wenused extensive equilibrium molecular dynamics simulations, potential of mean force (PMF) computations,nand quasi-harmonic analysis of the LeuT transporter with and without sodium ion bound at the Na2 site tondelineate the role of this site in the conformational dynamics of the protein. PMF computations show that innpresence of the sodiumion inNa2 the conserved T354 residue is locked into a single rotameric state in contrastnto two degenerate states available in the absence of ion inNa2.Molecular dynamics (MD) simulations suggestnthe formation of a stable water wire fromthe cytoplasmto theNa2 site in the occluded state. It is plausible thatnlocal hydration plays an important role in transport cycle facilitating release of the ion from Na2. Annunbinding of the ion fromtheNa2 site leads to a tightening of the extracellular thin gates and a destabilizationnof the intracellular thin gate and thus may promote an unbinding of the cotransported substrate. The studynlends additional support to the hypothesis that one of the main drivers in the transport cycle of Na-couplednsecondary transporters is the binding of the Na2 ion that controls dynamical equilibrium between an inward-nfacing to an outward-facing conformation
机译：钠偶联的二级转运蛋白的晶体学研究的最新进展尚未揭示离子和溶质结合的结构组织中的惊人相似之处。先前的报道暗示，神经递质钠转运蛋白（NSS）亮氨酸转运蛋白（LeuT）中的Na2钠结合位点在许多远亲家族的钠/质子偶联的二级转运蛋白中是保守的。该位点涉及通过很大程度上未知的机制受易位溶质和离子的结合和释放控制的构象动力学。在这项研究中，使用了广泛的平衡分子动力学模拟，潜在平均力（PMF）计算，在Na2位点上结合和不结合钠离子的LeuT转运蛋白的nand准谐波分析，描绘了该位点在构象动力学中的作用蛋白质。 PMF计算表明，在Na2中不存在钠离子时，保守的T354残基被锁定为单个旋转异构体状态，与在Na2中不存在离子时可得到的两个简并状态形成对比。处于封闭状态。可能是局部水合作用在运输循环中起着重要作用，促进了Na2离子的释放。来自Na 2位点的离子的解除结合导致细胞外薄门的收紧和细胞内薄门的不稳定，因此可以促进共转运底物的解除结合。该研究为以下假设提供了额外的支持：在Na耦合次生转运体的运输循环中，主要驱动因素之一是Na2离子的结合，该Na2离子控制着内向构象与外向构象之间的动态平衡。

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  • 来源
    《Biochemistry》 |2011年第11期|p.1848-1856|共9页
  • 作者

    Chunfeng Zhao and Sergei Yu. Noskov;

  • 作者单位

    Institute for Biocomplexity and Informatics and Department of Biological Sciences, University of Calgary, 2500 University Drive,BI558, Calgary, Alberta, Canada T2N 1N4;

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