HU multimerization shift controls nucleoid compaction.
HU multimerization shift controls nucleoid compaction.
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DOI：
10.1126/sciadv.1600650
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发表时间：
2016-07
期刊：
影响因子：
13.6
通讯作者：
Adhya S
中科院分区：
文献类型：
--
作者：
Hammel M;Amlanjyoti D;Reyes FE;Chen JH;Parpana R;Tang HY;Larabell CA;Tainer JA;Adhya S
HU网络控制染色质样DNA压缩，以同步细菌对发病机制和变化环境的反应。控制功能性细菌染色体（类核）压缩和组织的分子机制令人惊讶地神秘，但部分取决于保守的组蛋白样蛋白HUαα和HUαβ及其相互作用，这些相互作用跨越从蛋白质-DNA复合物到细菌染色体和类核结构的纳米尺度和中尺度。我们确定了这些染色体相关蛋白质与天然双链DNA复合的晶体结构。HUαα和HUαβ不同的DNA结合模式阐明了细菌染色体包装的基本特征，这些特征调节基因转录。通过结合晶体结构和溶液X射线散射结果，我们确定了HU-DNA核蛋白在接近生理条件下的溶液中的结构。这些大分子构象和相互作用导致基于在HUβ和异位HUα38表达后通过软X射线断层扫描对天然未标记类核的体内成像的细胞水平的收缩。电荷改变的HUαα-DNA复合物的结构表征揭示了一种适合于浓缩类核和将非侵入性大肠杆菌重编程为侵入性形式的HU分子开关。集体的研究结果表明，网络和合作和非合作DNA依赖的HU多聚化之间的转变控制DNA压缩和超螺旋独立的细胞拓扑异构酶活性。通过整合从蛋白质-DNA复合物到细菌染色体和类核结构的X射线晶体结构、X射线散射、突变测试和X射线成像，我们表明，定义的动态HU相互作用网络可以促进类核重组和转录调控作为有效的一般微生物机制，以帮助同步对细胞周期、环境变化和发病机制的遗传反应。
HU networks control chromatin-like DNA compaction to synchronize bacterial responses for pathogenesis and changing environments. Molecular mechanisms controlling functional bacterial chromosome (nucleoid) compaction and organization are surprisingly enigmatic but partly depend on conserved, histone-like proteins HUαα and HUαβ and their interactions that span the nanoscale and mesoscale from protein-DNA complexes to the bacterial chromosome and nucleoid structure. We determined the crystal structures of these chromosome-associated proteins in complex with native duplex DNA. Distinct DNA binding modes of HUαα and HUαβ elucidate fundamental features of bacterial chromosome packing that regulate gene transcription. By combining crystal structures with solution x-ray scattering results, we determined architectures of HU-DNA nucleoproteins in solution under near-physiological conditions. These macromolecular conformations and interactions result in contraction at the cellular level based on in vivo imaging of native unlabeled nucleoid by soft x-ray tomography upon HUβ and ectopic HUα38 expression. Structural characterization of charge-altered HUαα-DNA complexes reveals an HU molecular switch that is suitable for condensing nucleoid and reprogramming noninvasive Escherichia coli into an invasive form. Collective findings suggest that shifts between networking and cooperative and noncooperative DNA-dependent HU multimerization control DNA compaction and supercoiling independently of cellular topoisomerase activity. By integrating x-ray crystal structures, x-ray scattering, mutational tests, and x-ray imaging that span from protein-DNA complexes to the bacterial chromosome and nucleoid structure, we show that defined dynamic HU interaction networks can promote nucleoid reorganization and transcriptional regulation as efficient general microbial mechanisms to help synchronize genetic responses to cell cycle, changing environments, and pathogenesis.