Department of Biochemistry, Groningen Institute of Biomolecular Sciences & Biotechnology, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Commun Biol. 2024 May 21;7(1):610. doi: 10.1038/s42003-024-06295-2.
The processes of nutrient uptake and signal sensing are crucial for microbial survival and adaptation. Membrane-embedded proteins involved in these functions (transporters and receptors) are commonly regarded as unrelated in terms of sequence, structure, mechanism of action and evolutionary history. Here, we analyze the protein structural universe using recently developed artificial intelligence-based structure prediction tools, and find an unexpected link between prominent groups of microbial transporters and receptors. The so-called S-components of Energy-Coupling Factor (ECF) transporters, and the membrane domains of sensor histidine kinases of the 5TMR cluster share a structural fold. The discovery of their relatedness manifests a widespread case of prokaryotic "transceptors" (related proteins with transport or receptor function), showcases how artificial intelligence-based structure predictions reveal unchartered evolutionary connections between proteins, and provides new avenues for engineering transport and signaling functions in bacteria.
养分摄取和信号感应过程对于微生物的生存和适应至关重要。涉及这些功能的膜嵌入蛋白（转运体和受体）在序列、结构、作用机制和进化历史方面通常被认为是不相关的。在这里，我们使用最近开发的基于人工智能的结构预测工具来分析蛋白质结构宇宙，发现了微生物转运体和受体中两个显著群组之间的意外联系。能量偶联因子（ECF）转运体的所谓 S 成分和 5TMR 簇的传感器组氨酸激酶的膜结构域具有相同的结构折叠。它们相关性的发现体现了广泛存在的原核“转受体”（具有转运或受体功能的相关蛋白）的情况，展示了基于人工智能的结构预测如何揭示蛋白质之间未知的进化联系，并为细菌的转运和信号功能工程提供了新途径。
