The recently discovered SWEET (Sugar Will Eventually be Exported Transporter) proteins are involved in the selective transport of monosaccharides and disaccharides. The prokaryotic counterparts, semiSWEETs, form dimers with each monomer forming a triple-helix transmembrane bundle (THB). The longer eukaryotic SWEETs have seven transmembrane helices with two THBs and a linker helix. Structures of semiSWEETs/SWEETs have been determined experimentally. Experimental studies revealed the role of plant SWEETs in vital physiological processes and identified residues responsible for substrate selectivity. However, SWEETs/semiSWEETs from metazoans and bacteria are not characterized. In this study, we used structure-based sequence alignment and compared more than 2000 SWEET/semiSWEETs from four different taxonomic groups. Conservation of residue/chemical property was examined at all positions. Properties of clades/subclades of phylogenetic trees from each taxonomic group were analyzed. Conservation pattern of known residues in the selectivity-filter was used to predict the substrate preference of plant SWEETs and some clusters of metazoans and bacteria. Some residues at the gating and substrate-binding regions, pore-facing positions and at the helix–helix interface are conserved across all taxonomic groups. Conservation of polar/charged residues at specific pore-facing positions, helix–helix interface and in loops seems to be unique for plant SWEETs. Overall, the number of conserved residues is less in metazoan SWEETs. Plant and metazoan SWEETs exhibit high conservation of four and three proline residues respectively in “proline tetrad.” Further experimental studies can validate the predicted substrate selectivity and significance of conserved polar/charged/aromatic residues at structurally and functionally important positions of SWEETs/semiSWEETs in plants, metazoans and bacteria.

中文翻译：

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四个分类群的 SWEET/semiSWEET 同源物中的底物选择性和独特序列特征：序列分析和系统发育研究

最近发现的SWEET（糖最终将被输出转运蛋白）蛋白参与单糖和二糖的选择性转运。原核对应物 semiSWEET 形成二聚体，每个单体形成三螺旋跨膜束 (THB)。较长的真核 SWEET 有七个跨膜螺旋，其中有两个 THB 和一个连接螺旋。semiSWEET/SWEET 的结构已通过实验确定。实验研究揭示了植物 SWEET 在重要生理过程中的作用，并确定了负责底物选择性的残基。然而，来自后生动物和细菌的 SWEET/semiSWEET 尚未得到表征。在这项研究中，我们使用基于结构的序列比对，比较了来自四个不同分类组的 2000 多个 SWEET/semiSWEET。在所有位置检查残留物/化学性质的保存。分析了每个分类组的系统发育树的进化枝/亚进化枝的特性。选择性过滤器中已知残留物的保守模式用于预测植物 SWEET 以及一些后生动物和细菌簇的底物偏好。门控和底物结合区域、面向孔的位置以及螺旋-螺旋界面处的一些残基在所有分类群中都是保守的。在面向孔的特定位置、螺旋-螺旋界面和环中极性/带电残基的保守性似乎对于植物 SWEET 来说是独特的。总体而言，后生动物 SWEET 中保守残基的数量较少。植物和后生动物 SWEET 在“脯氨酸四分体”中分别表现出四个和三个脯氨酸残基的高度保守性。进一步的实验研究可以验证植物、后生动物和细菌中 SWEET/semiSWEET 结构和功能重要位置上保守的极性/带电/芳香族残基的预测底物选择性和重要性。