Origin and evolution of transporter substrate specificity within the NPF family.
Origin and evolution of transporter substrate specificity within the NPF family.
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DOI：
10.7554/elife.19466
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发表时间：
2017-03-03
期刊：
影响因子：
7.7
通讯作者：
Halkier BA
中科院分区：
文献类型：
--
作者：
Jørgensen ME;Xu D;Crocoll C;Ernst HA;Ramírez D;Motawia MS;Olsen CE;Mirza O;Nour-Eldin HH;Halkier BA
尽管代谢物及其转运体的底物特异性存在巨大的多样性，但人们对转运体底物特异性的进化如何通过生物合成途径的进化与底物的出现联系知之甚少。转运体对最近进化的芥子油苷特征的特异性显示在芥子油苷生物合成出现之前就已经进化。此外，研究人员发现，普遍存在的NRT1/PTR家族（NPF）的硫代葡萄糖苷转运蛋白可能是从在2500多种芸苔属植物以外的物种中发现的祖先产氰葡萄糖苷转运蛋白进化而来的。从木薯到拟南芥的系统发育谱系的同源生物化学特征表明，转运蛋白的电原性变化伴随着底物特异性的变化。将转运体底物特异性的进化路径与生物合成途径的进化路径联系起来，举例说明转运体底物特异性是如何随着新的生物合成途径的出现而产生和进化的。所有的活细胞都被膜包围着，保护它们不受外界环境的影响。细胞膜上含有一种叫做转运蛋白的蛋白质，这种蛋白质将营养物质和其他分子（称为底物）穿过细胞膜。各种各样的转运蛋白已经进化到可以运输自然界中发现的成千上万种不同的底物。植物细胞制造许多不同的化合物来保护自己免受病虫害的侵害。一组被称为NPF家族的转运蛋白将这些化合物穿过细胞的外层膜。它们运输的底物类型在不同的植物中是不同的。例如，在木薯中，NPF转运蛋白会移动一种叫氰苷的化合物，这种化合物对人类和其他动物有毒。另一方面，另一种叫做拟南芥的植物中的NPF转运蛋白可以移动一种叫硫代葡萄糖苷的苦味化合物。植物中产生硫代葡萄糖苷的过程是从产生氰糖苷的过程进化而来的。转运蛋白能在新底物首次出现之前或之后进化出移动新底物的能力吗？为了回答这个问题，Jørgensen等人研究了拟南芥、木薯和另一种叫做木瓜的植物中的NPF家族，这种植物既能产生氰糖苷，也能产生硫代葡萄糖苷。实验表明，在植物进化出制造硫代葡萄糖苷的能力之前，NPF转运体就已经进化出了能够同时移动含氰葡萄糖苷和硫代葡萄糖苷的转运体。在后来的进化中，这些多特异性转运蛋白专门用于运输硫代葡萄糖苷。Jørgensen等人也表明，早期的硫代葡萄糖苷转运体可以运输多种硫代葡萄糖苷，但后来进化为只运输特定类型的硫代葡萄糖苷。这些发现显示了细胞中的转运蛋白和合成化合物的过程是如何共同进化的。未来的挑战将是了解转运蛋白的分子变化，使其对某种底物具有特异性。这可能有助于研究人员开发新的方法，通过控制化合物的运输方式来控制我们吃的作物中有毒化合物的数量。
Despite vast diversity in metabolites and the matching substrate specificity of their transporters, little is known about how evolution of transporter substrate specificities is linked to emergence of substrates via evolution of biosynthetic pathways. Transporter specificity towards the recently evolved glucosinolates characteristic of Brassicales is shown to evolve prior to emergence of glucosinolate biosynthesis. Furthermore, we show that glucosinolate transporters belonging to the ubiquitous NRT1/PTR FAMILY (NPF) likely evolved from transporters of the ancestral cyanogenic glucosides found across more than 2500 species outside of the Brassicales. Biochemical characterization of orthologs along the phylogenetic lineage from cassava to A. thaliana, suggests that alterations in the electrogenicity of the transporters accompanied changes in substrate specificity. Linking the evolutionary path of transporter substrate specificities to that of the biosynthetic pathways, exemplify how transporter substrate specificities originate and evolve as new biosynthesis pathways emerge. All living cells are surrounded by membranes that protect them from the external environment. The membrane contains proteins called transporters, which move nutrients and other molecules (known as substrates) across the membrane. A variety of transporters have evolved to move the hundreds of thousands of different substrates found in nature. Plant cells make many different compounds to protect themselves from pests and diseases. A group of transporters known as the NPF family move some of these compounds across the cells outer membrane. The types of substrates they transport vary in different plants. In cassava, for example, NPF transporters move compounds called cyanogenic glucosides, which are poisonous to humans and other animals. On the other hand, NPF transporters in another plant called Arabidopsis thaliana can move bitter-tasting compounds called glucosinolates. The process that makes glucosinolates in plants evolved from the process that makes cyanogenic glucosides. Can transporters evolve the ability to move a new substrate before or after that substrate first appears? To answer this question, Jørgensen et al. studied the NPF family in A. thaliana, cassava and another plant called papaya that makes both cyanogenic glucosides and glucosinolates. The experiments suggest that NPF transporters able to move both cyanogenic glucosides and glucosinolates evolved before plants evolved the ability to make glucosinolates. Later in evolution, these multi-specific transporters specialized to only move glucosinolates. Jørgensen et al. also show that early glucosinolate transporters could move a broad variety of glucosinolates but later evolved to only transport particular types. These findings show how transporters and the processes that make compounds in cells may evolve together. A future challenge will be to understand the molecular changes in a transporter that make it specific for a certain substrate. This may help researchers to develop new ways of controlling the amount of toxic compounds in crops we eat by manipulating how the compounds are transported.