Schumacher Maria A, Zeng Wenjie, Findlay Kim C, Buttner Mark J, Brennan Richard G, Tschowri Natalia
Department of Biochemistry, Duke University School of Medicine, Durham, NC 27701, USA.
Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
Nucleic Acids Res. 2017 Jun 20;45(11):6923-6933. doi: 10.1093/nar/gkx287.
Streptomyces are ubiquitous soil bacteria that undergo a complex developmental transition coinciding with their production of antibiotics. This transition is controlled by binding of a novel tetrameric form of the second messenger, 3΄-5΄ cyclic diguanylic acid (c-di-GMP) to the master repressor, BldD. In all domains of life, nucleotide-based second messengers allow a rapid integration of external and internal signals into regulatory pathways that control cellular responses to changing conditions. c-di-GMP can assume alternative oligomeric states to effect different functions, binding to effector proteins as monomers, intercalated dimers or, uniquely in the case of BldD, as a tetramer. However, at physiological concentrations c-di-GMP is a monomer and little is known about how higher oligomeric complexes assemble on effector proteins and if intermediates in assembly pathways have regulatory significance. Here, we show that c-di-GMP binds BldD using an ordered, sequential mechanism and that BldD function necessitates the assembly of the BldD2-(c-di-GMP)4 complex.
链霉菌是普遍存在于土壤中的细菌，它们在产生抗生素的同时会经历复杂的发育转变。这种转变是由新型四聚体形式的第二信使3΄-5΄环二鸟苷酸（c-di-GMP）与主要阻遏蛋白BldD结合来控制的。在所有生命领域中，基于核苷酸的第二信使能使外部和内部信号快速整合到调控途径中，这些途径控制细胞对不断变化的环境条件的反应。c-di-GMP可以呈现不同的寡聚状态以实现不同功能，作为单体、插入二聚体或（在BldD的情况下独特地）作为四聚体与效应蛋白结合。然而，在生理浓度下，c-di-GMP是单体，关于更高阶寡聚复合物如何在效应蛋白上组装以及组装途径中的中间体是否具有调控意义，人们了解甚少。在这里，我们表明c-di-GMP通过有序的顺序机制结合BldD，并且BldD的功能需要组装BldD2-(c-di-GMP)4复合物。
