Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom.
Department of Animal and Plant Sciences, University of Sheffield, Sheffield, United Kingdom.
Front Cell Infect Microbiol. 2018 Feb 12;8:33. doi: 10.3389/fcimb.2018.00033. eCollection 2018.
The ability to efficiently scavenge nutrients in the host is essential for the viability of any pathogen. All catabolic pathways must begin with the transport of substrate from the environment through the cytoplasmic membrane, a role executed by membrane transporters. Although several classes of cytoplasmic membrane transporters are described, high-affinity uptake of substrates occurs through Solute Binding-Protein (SBP) dependent systems. Three families of SBP dependant transporters are known; the primary ATP-binding cassette (ABC) transporters, and the secondary Tripartite ATP-independent periplasmic (TRAP) transporters and Tripartite Tricarboxylate Transporters (TTT). Far less well understood than the ABC family, the TRAP transporters are found to be abundant among bacteria from marine environments, and the TTT transporters are the most abundant family of proteins in many species of β-proteobacteria. In this review, recent knowledge about these families is covered, with emphasis on their physiological and structural mechanisms, relating to several examples of relevant uptake systems in pathogenicity and colonization, using the SiaPQM sialic acid uptake system from and the TctCBA citrate uptake system of as the prototypes for the TRAP and TTT transporters, respectively. High-throughput analysis of SBPs has recently expanded considerably the range of putative substrates known for TRAP transporters, while the repertoire for the TTT family has yet to be fully explored but both types of systems most commonly transport carboxylates. Specialized spectroscopic techniques and site-directed mutagenesis have enriched our knowledge of the way TRAP binding proteins capture their substrate, while structural comparisons show conserved regions for substrate coordination in both families. Genomic and protein sequence analyses show TTT SBP genes are strikingly overrepresented in some bacteria, especially in the β-proteobacteria and some α-proteobacteria. The reasons for this are not clear but might be related to a role for these proteins in signaling rather than transport.
有效地从宿主中摄取营养对于任何病原体的存活都是至关重要的。所有的分解代谢途径都必须从环境中开始，通过细胞质膜将基质转运到细胞质中，这一功能由膜转运蛋白来执行。尽管已经描述了几类细胞质膜转运蛋白，但高亲和力的底物摄取是通过溶质结合蛋白（SBP）依赖性系统实现的。已知有三种 SBP 依赖性转运蛋白家族；主要的 ATP 结合盒（ABC）转运蛋白，以及次要的三部分 ATP 独立周质（TRAP）转运蛋白和三部分三羧酸转运蛋白（TTT）。与 ABC 家族相比，TRAP 转运蛋白的了解要少得多，它们在海洋环境中的细菌中大量存在，而 TTT 转运蛋白是许多β-变形菌物种中最丰富的蛋白质家族。在这篇综述中，涵盖了最近关于这些家族的知识，重点介绍了它们的生理和结构机制，涉及到致病性和定植中的几个相关摄取系统的例子，使用 SiaPQM 唾液酸摄取系统和 TctCBA 柠檬酸摄取系统分别作为 TRAP 和 TTT 转运蛋白的原型。最近，对 SBP 的高通量分析大大扩展了 TRAP 转运蛋白已知的潜在底物范围，而 TTT 家族的底物范围尚未得到充分探索，但这两种类型的系统最常运输羧酸。专门的光谱技术和定点突变丰富了我们对 TRAP 结合蛋白捕获其底物的方式的认识，而结构比较显示了两个家族中都有用于底物协调的保守区域。基因组和蛋白质序列分析表明，TTT SBP 基因在某些细菌中，特别是在β-变形菌和一些α-变形菌中，显著过表达。原因尚不清楚，但可能与这些蛋白质在信号传递而不是运输中的作用有关。
