Ion-coupled secondary transport is utilized by a broad range of integral membrane proteins to catalyze the energetically unfavorable movement of solute molecules across a lipid bilayer. Members of the solute carrier 6 (SLC6) family, present in both prokaryotes and eukaryotes, are sodium-coupled symporters that play crucial roles in processes as diverse as nutrient uptake and neurotransmitter clearance. The crystal structure of LeuT, a bacterial member of this family, provided the first atomic-level glimpse into overall architecture, pinpointed the substrate and sodium binding sites and implicated candidate helices and residues in the "gating" conformational changes that accompany ion binding and release. The structure is consistent with a wealth of elegant biochemical data on the eukaryotic counterparts and has for the first time permitted the construction of accurate homology models that can be directly tested experimentally. Sequence identity is especially high near the substrate and sodium binding sites and, thus, molecular insights within these regions have been substantial. However, there are several topics relevant to transport mechanism, inhibition and regulation that structure/function studies of LeuT cannot adequately address, suggesting the need for a eukaryotic transporter crystal structure.

中文翻译：

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LeuT：通往真核神经递质转运体结构的原核垫脚石。

离子耦合的二级转运被广泛的完整膜蛋白利用，以催化溶质分子穿过脂质双层的能量不利运动。溶质载体 6 (SLC6) 家族的成员存在于原核生物和真核生物中，是钠偶联同向转运体，在营养吸收和神经递质清除等多种过程中发挥着至关重要的作用。该家族细菌成员 LeuT 的晶体结构提供了对整体结构的第一个原子级一瞥，确定了底物和钠结合位点，并暗示了伴随离子结合和释放的“门控”构象变化中的候选螺旋和残基. 该结构与真核生物对应物的大量优雅生化数据一致，并且首次允许构建可直接进行实验测试的准确同源模型。底物和钠结合位点附近的序列同一性特别高，因此，这些区域内的分子洞察力非常大。然而，有几个与 LeuT 的结构/功能研究无法充分解决的与转运机制、抑制和调节相关的主题，表明需要真核转运蛋白晶体结构。