Department of Biotechnology, Bhupat & Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, India.
Center for Biomolecular Structure and Organization, Department of Chemistry & Biochemistry, University of Maryland, College Park, MD, 20742, USA.
Nat Commun. 2019 Apr 30;10(1):1995. doi: 10.1038/s41467-019-10002-9.
Uropathogenic E. coli experience a wide range of osmolarity conditions before and after successful infection. Stress-responsive regulatory proteins in bacteria, particularly proteins of the Hha family and H-NS, a transcription repressor, sense such osmolarity changes and regulate transcription through unknown mechanisms. Here we use an array of experimental probes complemented by molecular simulations to show that Cnu, a member of the Hha protein family, acts as an exquisite molecular sensor of solvent ionic strength. The osmosensory behavior of Cnu involves a fine-tuned modulation of disorder in the fourth helix and the three-dimensional structure in a graded manner. Order-disorder transitions in H-NS act synergistically with molecular swelling of Cnu contributing to a salt-driven switch in binding cooperativity. Thus, sensitivity to ambient conditions can be imprinted at the molecular level by tuning not just the degree of order in the protein conformational ensemble but also through population redistributions of higher-order molecular complexes.
尿路致病性大肠杆菌在成功感染前后会经历多种渗透压条件。细菌中的应激反应调节蛋白，特别是 Hha 家族蛋白和转录抑制剂 H-NS，能够感知这种渗透压变化，并通过未知机制调节转录。在这里，我们使用一系列实验探针并结合分子模拟，表明 Hha 蛋白家族的成员 Cnu 是溶剂离子强度的精确分子传感器。Cnu 的渗透压感应行为涉及到第四螺旋和三维结构的精细调控，以分级方式实现无序的精细调节。H-NS 的有序-无序转变与 Cnu 的分子膨胀协同作用，导致结合协同性的盐驱动开关。因此，通过调节蛋白质构象总体中有序的程度以及通过更高阶分子复合物的种群再分布，可以在分子水平上对环境条件的敏感性进行“印记”。
