Structure of a eukaryotic SWEET transporter in a homotrimeric complex.
Structure of a eukaryotic SWEET transporter in a homotrimeric complex.
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同源三聚体复合物中真核 SWEET 转运蛋白的结构
DOI：
10.1038/nature15391
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发表时间：
2015-11-12
期刊：
影响因子：
64.8
通讯作者：
Feng L
中科院分区：
文献类型：
--
作者：
Tao Y;Cheung LS;Li S;Eom JS;Chen LQ;Xu Y;Perry K;Frommer WB;Feng L
真核生物依赖于以糖的形式在器官之间有效分配能量和碳骨架。动物中的葡萄糖和植物中的蔗糖是主要的分布形式。细胞糖的摄取和释放需要囊泡和/或质膜转运蛋白。人类和植物使用来自三个超家族的蛋白质进行糖易位：主要促进子超家族 (MFS)、钠溶质同向转运蛋白家族 (SSF；仅在动物界) 和 SWEETs,,,,。甜食携带单糖和二糖穿过液泡或质膜。植物 SWEET 在区室、细胞和器官之间的糖转移中发挥着关键作用，特别是在花蜜分泌、长距离转移的韧皮部装载、花粉营养和种子灌浆方面。植物甜食可能通过受感染细胞的糖泄漏而导致病原体易感性。液泡拟南芥AtSWEET2将糖隔离在根液泡中；功能丧失突变体表现出对腐霉感染的易感性增加。在这里，我们展示了其直系同源物，来自水稻（Oryza sativa）的液泡葡萄糖转运蛋白 OsSWEET2b，由一对不对称的三螺旋束组成，通过反向接头跨膜螺旋（TM4）连接以创建易位途径。结构和生化分析显示 OsSWEET2b 处于明显的向内（胞质）开放状态，形成同聚三聚体。 TM4 与原聚体中的第一个三螺旋束紧密相互作用，并介导原聚体之间的关键接触。来自拟南芥的近亲旁系同源物 SWEET1 的结构引导诱变鉴定了底物易位和原体串扰中的关键残基。深入了解 SWEET 的结构-功能关系对于理解真核 SWEET 的转运机制很有价值，并且可能有助于工程糖通量。
Eukaryotes rely on efficient distribution of energy and carbon skeletons between organs in the form of sugars. Glucose in animals and sucrose in plants serve as the dominant distribution forms. Cellular sugar uptake and release require vesicular and/or plasma membrane transport proteins. Humans and plants use proteins from three superfamilies for sugar translocation: the major facilitator superfamily (MFS), the sodium solute symporter family (SSF; only in the animal kingdom), and SWEETs,,,,. SWEETs carry mono- and disaccharides across vacuolar or plasma membranes. Plant SWEETs play key roles in sugar translocation between compartments, cells, and organs, notably in nectar secretion, phloem loading for long distance translocation, pollen nutrition, and seed filling. Plant SWEETs cause pathogen susceptibility possibly by sugar leakage from infected cells,,. The vacuolarArabidopsis thalianaAtSWEET2 sequesters sugars in root vacuoles; loss-of-function mutants show increased susceptibility toPythiuminfection. Here we show that its orthologue, the vacuolar glucose transporter OsSWEET2b from rice (Oryza sativa), consists of an asymmetrical pair of triple-helix bundles, connected by an inversion linker transmembrane helix (TM4) to create the translocation pathway. Structural and biochemical analyses show OsSWEET2b in an apparent inward (cytosolic) open state forming homomeric trimers. TM4 tightly interacts with the first triple-helix bundle within a protomer and mediates key contacts among protomers. Structure-guided mutagenesis of the close paralogue SWEET1 fromArabidopsisidentified key residues in substrate translocation and protomer crosstalk. Insights into the structure–function relationship of SWEETs are valuable for understanding the transport mechanism of eukaryotic SWEETs and may be useful for engineering sugar flux.