H-NS family proteins, bacterial xenogeneic silencers, play central roles in genome organization and in the regulation of foreign genes. It is thought that gene repression is directly dependent on the DNA binding modes of H-NS family proteins. These proteins form lateral protofilaments along DNA. Under specific environmental conditions they switch to bridging two DNA duplexes. This switching is a direct effect of environmental conditions on electrostatic interactions between the oppositely charged DNA binding and N-terminal domains of H-NS proteins. The Pseudomonas lytic phage LUZ24 encodes the protein gp4, which modulates the DNA binding and function of the H-NS family protein MvaT of Pseudomonas aeruginosa. However, the mechanism by which gp4 affects MvaT activity remains elusive. In this study, we show that gp4 specifically interferes with the formation and stability of the bridged MvaT–DNA complex. Structural investigations suggest that gp4 acts as an ‘electrostatic zipper’ between the oppositely charged domains of MvaT protomers, and stabilizes a structure resembling their ‘half-open’ conformation, resulting in relief of gene silencing and adverse effects on P. aeruginosa growth. The ability to control H-NS conformation and thereby its impact on global gene regulation and growth might open new avenues to fight Pseudomonas multidrug resistance.

中文翻译：

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噬菌体蛋白对 H-NS 蛋白的新型抗抑制机制

H-NS 家族蛋白，细菌异种消音器，在基因组组织和外源基因调控中发挥核心作用。人们认为基因抑制直接依赖于 H-NS 家族蛋白的 DNA 结合模式。这些蛋白质沿着 DNA 形成横向原丝。在特定的环境条件下，它们转而桥接两个 DNA 双链体。这种转换是环境条件对带相反电荷的 DNA 结合与 H-NS 蛋白的 N 端结构域之间的静电相互作用的直接影响。假单胞菌裂解噬菌体 LUZ24 编码蛋白 gp4，它调节铜绿假单胞菌 H-NS 家族蛋白 MvaT 的 DNA 结合和功能。然而，gp4 影响 MvaT 活性的机制仍然难以捉摸。在这项研究中，我们表明gp4特异性干扰桥接MvaT-DNA复合物的形成和稳定性。结构研究表明，gp4 在 MvaT 原体的带相反电荷的结构域之间充当“静电拉链”，并稳定类似于其“半开放”构象的结构，从而缓解基因沉默和对铜绿假单胞菌生长的不利影响。控制 H-NS 构象的能力及其对全球基因调控和生长的影响可能会开辟对抗假单胞菌多药耐药性的新途径。从而减轻基因沉默和对铜绿假单胞菌生长的不利影响。控制 H-NS 构象的能力及其对全球基因调控和生长的影响可能会开辟对抗假单胞菌多药耐药性的新途径。从而减轻基因沉默和对铜绿假单胞菌生长的不利影响。控制 H-NS 构象的能力及其对全球基因调控和生长的影响可能会开辟对抗假单胞菌多药耐药性的新途径。