Vollum Institute, Oregon Health and Science University, Portland, Oregon, USA.
Channels (Austin). 2008 Sep-Oct;2(5):380-9. doi: 10.4161/chan.2.5.6904.
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.
离子耦联的次级转运被广泛的跨膜蛋白所利用，以催化溶质分子穿过脂双层的不利能量移动。溶质载体 6（SLC6）家族的成员存在于原核生物和真核生物中，是钠偶联的协同转运蛋白，在营养物质摄取和神经递质清除等多种过程中发挥着关键作用。该家族中细菌成员 LeuT 的晶体结构提供了对整体结构的第一个原子水平的见解，确定了底物和钠离子结合位点，并暗示候选螺旋和残基参与伴随离子结合和释放的“门控”构象变化。该结构与大量关于真核对应物的优雅生化数据一致，并首次允许构建可直接进行实验测试的准确同源模型。在底物和钠离子结合位点附近的序列同一性特别高，因此，这些区域的分子见解是实质性的。然而，有几个与转运机制、抑制和调节相关的主题，LeuT 的结构/功能研究无法充分解决，这表明需要一个真核转运蛋白的晶体结构。
