Structure of eukaryotic purine/H(+) symporter UapA suggests a role for homodimerization in transport activity.
Structure of eukaryotic purine/H(+) symporter UapA suggests a role for homodimerization in transport activity.
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DOI：
10.1038/ncomms11336
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发表时间：
2016-04-18
影响因子：
16.6
通讯作者：
Byrne B
中科院分区：
文献类型：
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作者：
Alguel Y;Amillis S;Leung J;Lambrinidis G;Capaldi S;Scull NJ;Craven G;Iwata S;Armstrong A;Mikros E;Diallinas G;Cameron AD;Byrne B
尿酸/黄嘌呤H+转运蛋白UapA是丝状真菌Nidulans的一种高亲和力的嘌呤转运蛋白。在这里，我们提出了一个遗传稳定版本的UapA(UapA-G411VΔ1-11)与黄嘌呤的络合物的晶体结构。UapA由核心区和门区两个结构域组成，与之前已破译的尿嘧啶转运蛋白UraA类似，属于同一家族。结构显示UapA呈内向构象，黄嘌呤与核心区的残基结合。与被观察到是单体的UraA不同，UapA在晶体中形成二聚体，二聚体相互作用仅通过门区形成。对显性负突变体的分析与二聚化在运输中起关键作用是一致的。我们假设UapA使用一种电梯运输机制，很可能与其他结构上同源的转运蛋白共享，包括阴离子交换器和Prestin。UapA是一种丝状真菌的尿酸/黄嘌呤H+转运蛋白。在这里，作者解决了转运蛋白的晶体结构与黄嘌呤的络合物，揭示了它是一个二聚体，这种同源二聚被认为是重要的功能。
The uric acid/xanthine H+ symporter, UapA, is a high-affinity purine transporter from the filamentous fungus Aspergillus nidulans. Here we present the crystal structure of a genetically stabilized version of UapA (UapA-G411VΔ1–11) in complex with xanthine. UapA is formed from two domains, a core domain and a gate domain, similar to the previously solved uracil transporter UraA, which belongs to the same family. The structure shows UapA in an inward-facing conformation with xanthine bound to residues in the core domain. Unlike UraA, which was observed to be a monomer, UapA forms a dimer in the crystals with dimer interactions formed exclusively through the gate domain. Analysis of dominant negative mutants is consistent with dimerization playing a key role in transport. We postulate that UapA uses an elevator transport mechanism likely to be shared with other structurally homologous transporters including anion exchangers and prestin. UapA is a uric acid/xanthine H+ symporter from a filamentous fungus. Here, the authors solve the crystal structure of the transporter in complex with xanthine revealing it to be a dimer, and this homodimerisation is proposed to be important for function.