A Novel Class of Modular Transporters for Vitamins in Prokaryotes
A Novel Class of Modular Transporters for Vitamins in Prokaryotes
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DOI：
10.1128/jb.01208-08
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发表时间：
2009-01-01
影响因子：
3.2
通讯作者：
Eitinger, Thomas
中科院分区：
文献类型：
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作者：
Rodionov, Dmitry A.;Hebbeln, Peter;Eitinger, Thomas
大量营养物质和代谢物跨细胞膜的特定且严格控制的运输对于所有生命形式都至关重要。然而，许多涉及的转运蛋白尚未被鉴定，包括各种人类病原体中的维生素转运蛋白，其生长严格依赖于维生素的吸收。对不断增长的微生物基因组集合的比较分析加上实验验证使得能够发现此类转运蛋白。在这里，我们使用这种方法在原核生物中发现了一类丰富的维生素转运蛋白，具有前所未有的结构。这些转运蛋白具有由保守的跨膜蛋白和两个核苷酸结合蛋白组成的能量耦合模块，类似于 ATP 结合盒 (ABC) 转运蛋白，但与 ABC 转运蛋白不同，它们使用小的整合膜蛋白来捕获特定底物。我们鉴定了这些底物捕获蛋白的 21 个家族，每个家族都具有通过基因组背景分析预测的不同特异性。大约一半的底物捕获蛋白（335 个案例）具有专用的供能模块，但在 459 个案例中，分布在近 100 种革兰氏阳性细菌（包括许多人类病原体）中，不同且不相关的底物捕获蛋白共享相同的能量耦合模块。实验证实了叶酸、硫胺素和核黄素转运蛋白能量耦合模块的共同使用。我们提议将新型膜转运蛋白命名为能量耦合因子转运蛋白。
The specific and tightly controlled transport of numerous nutrients and metabolites across cellular membranes is crucial to all forms of life. However, many of the transporter proteins involved have yet to be identified, including the vitamin transporters in various human pathogens, whose growth depends strictly on vitamin uptake. Comparative analysis of the ever-growing collection of microbial genomes coupled with experimental validation enables the discovery of such transporters. Here, we used this approach to discover an abundant class of vitamin transporters in prokaryotes with an unprecedented architecture. These transporters have energy-coupling modules comprised of a conserved transmembrane protein and two nucleotide binding proteins similar to those of ATP binding cassette (ABC) transporters, but unlike ABC transporters, they use small integral membrane proteins to capture specific substrates. We identified 21 families of these substrate capture proteins, each with a different specificity predicted by genome context analyses. Roughly half of the substrate capture proteins (335 cases) have a dedicated energizing module, but in 459 cases distributed among almost 100 gram-positive bacteria, including numerous human pathogens, different and unrelated substrate capture proteins share the same energy-coupling module. The shared use of energy-coupling modules was experimentally confirmed for folate, thiamine, and riboflavin transporters. We propose the name energy-coupling factor transporters for the new class of membrane transporters.