Novel anti-repression mechanism of H-NS proteins by a phage protein. Issue 18 (14th September 2021)

• Record Type: Journal Article
• Authors: Bdira, Fredj Ben; Erkelens, Amanda M; Qin, Liang; Volkov, Alexander N; Lippa, Andrew M; Bowring, Nicholas; Boyle, Aimee L; Ubbink, Marcellus; Dove, Simon L; Dame, Remus T
• Is Part Of: Nucleic acids research. Volume 49:Issue 18(2021)
• Page Start: 10770
• Page End: 10784
• Publication Date: 2021-09-14
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkab793
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: 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.