Chaves-Sanjuan Antonio, D'Abrosca Gianluca, Russo Veronica, van Erp Bert, Del Cont-Bernard Alessandro, Capelli Riccardo, Pirone Luciano, Slapakova Martina, Sgambati Domenico, Fattorusso Roberto, Isernia Carla, Russo Luigi, Barton Ian S, Roop Roy Martin, Pedone Emilia M, Bolognesi Martino, Dame Remus T, Pedone Paolo V, Nardini Marco, Malgieri Gaetano, Baglivo Ilaria
Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milano, Italy.
Fondazione Romeo e Enrica Invernizzi and NOLIMITS, University of Milan, Via Celoria 26, 20133 Milan, Italy.
Nucleic Acids Res. 2024 Dec 11;52(22):13945-13963. doi: 10.1093/nar/gkae1104.
The transcriptional regulator MucR from Brucella species controls the expression of many genes, including those involved in virulence, by binding AT-rich DNA regions. MucR and its homologs belong to the Ros/MucR family, whose members occur in α-proteobacteria. MucR is a recent addition to the family of histone-like nucleoid structuring (H-NS) proteins. Indeed, despite the lack of sequence homology, MucR bears many functional similarities with H-NS and H-NS-like proteins, structuring the bacterial genome and acting as global regulators of transcription. Here we present an integrated cryogenic electron microscopy (cryo-EM), nuclear magnetic resonance, modeling and biochemical study shedding light on the functional architecture of MucR from Brucella abortus and its homolog Ml5 from Mesorhizobium loti. We show that MucR and Ml5 fold in a circular quaternary assembly, which allows it to bridge and condense DNA by binding AT-rich sequences. Our results show that Ros/MucR family members are a novel type of H-NS-like proteins and, based on previous studies, provide a model connecting nucleoid structure and transcription regulation in α-proteobacteria.
布鲁氏菌属的转录调节因子MucR通过结合富含AT的DNA区域来控制许多基因的表达，包括那些与毒力相关的基因。MucR及其同源物属于Ros/MucR家族，该家族成员存在于α-变形杆菌中。MucR是类组蛋白核仁结构（H-NS）蛋白家族中的新成员。实际上，尽管缺乏序列同源性，但MucR与H-NS及类H-NS蛋白具有许多功能相似性，可构建细菌基因组并作为转录的全局调节因子。在此，我们展示了一项综合低温电子显微镜（cryo-EM）、核磁共振、建模和生化研究，该研究揭示了流产布鲁氏菌的MucR及其来自百脉根中生根瘤菌的同源物Ml5的功能结构。我们表明，MucR和Ml5以环状四级组装形式折叠，这使其能够通过结合富含AT的序列来桥接和凝聚DNA。我们的结果表明，Ros/MucR家族成员是一种新型的类H-NS蛋白，并基于先前的研究，提供了一个连接α-变形杆菌中核仁结构与转录调控的模型。
