Institut des Sciences du Végétal, CNRS, avenue de la terrasse, 91198, Gif-sur-Yvette, France.
Mol Microbiol. 2012 Dec;86(5):1085-99. doi: 10.1111/mmi.12043. Epub 2012 Oct 9.
GABA acts as an intercellular signal in eukaryotes and as an interspecies signal in host-microbe interactions. Structural characteristics of selective eukaryotic GABA receptors and bacterial GABA sensors are unknown. Here, we identified the selective GABA-binding protein, called Atu4243, in the plant pathogen Agrobacterium tumefaciens. A constructed atu4243 mutant was affected in GABA transport and in expression of the GABA-regulated functions, including aggressiveness on two plant hosts and degradation of the quorum-sensing signal. The GABA-bound Atu4243 structure at 1.28 Å reveals that GABA adopts a conformation never observed so far and interacts with two key residues, Arg(203) and Asp(226) of which the role in GABA binding and GABA signalling in Agrobacterium has been validated using appropriate mutants. The conformational GABA-analogue trans-4-aminocrotonic acid (TACA) antagonizes GABA activity, suggesting structural similarities between the binding sites of the bacterial sensor Atu4243 and mammalian GABA(C) receptors. Exploration of genomic databases reveals Atu4243 orthologues in several pathogenic and symbiotic proteobacteria, such as Rhizobium, Azospirillum, Burkholderia and Pseudomonas. Thus, this study establishes a structural basis for selective GABA sensors and offers opportunities for deciphering the role of the GABA-mediated communication in several host-pathogen interactions.
GABA 在真核生物中作为细胞间信号分子，在宿主-微生物相互作用中作为种间信号分子。选择性真核 GABA 受体和细菌 GABA 传感器的结构特征尚不清楚。在这里，我们在植物病原体根瘤农杆菌中鉴定了一种名为 Atu4243 的选择性 GABA 结合蛋白。构建的 atu4243 突变体在 GABA 转运和 GABA 调节功能的表达方面受到影响，包括在两种植物宿主上的侵袭性和群体感应信号的降解。在 1.28Å 的 GABA 结合 Atu4243 结构中，GABA 采用了一种迄今从未观察到的构象，并与两个关键残基相互作用，Arg（203）和 Asp（226），其在 GABA 结合和根瘤农杆菌中 GABA 信号传导中的作用已通过适当的突变体得到验证。构象 GABA 类似物反式-4-氨基-2-丁烯酸（TACA）拮抗 GABA 活性，表明细菌传感器 Atu4243 和哺乳动物 GABA（C）受体的结合位点之间存在结构相似性。对基因组数据库的探索揭示了 Atu4243 在几种致病和共生变形菌中的同源物，如根瘤菌、固氮螺菌、伯克霍尔德菌和假单胞菌。因此，本研究为选择性 GABA 传感器建立了结构基础，并为解析 GABA 介导的通讯在几种宿主-病原体相互作用中的作用提供了机会。
