Role of salt valency in the switch of H-NS proteins between DNA-bridging and DNA-stiffening modes

Abstract

This work investigates the interactions of H-NS proteins and bacterial genomic DNA through computer simulations performed with a coarse-grained model. The model was developed specifically to study the switch of H-NS proteins from the DNA-stiffening to the DNA-bridging mode, which has been observed repeatedly upon addition of multivalent cations to the buffer, but is still not understood. Unravelling the corresponding mechanism is all the more crucial, as the regulation properties of H-NS proteins, as well as other nucleoid proteins, are linked to their DNA-binding properties. The simulations reported here support a mechanism, according to which the primary role of multivalent cations consists in decreasing the strength of H-NS/DNA interactions compared to H-NS/H-NS interactions, with the latter ones becoming energetically favored with respect to the former ones above a certain threshold of the effective valency of the cations of the buffer. Below the threshold, H-NS dimers form filaments, which stretch along the DNA molecule but are quite inefficient in bridging genomically distant DNA sites (DNA-stiffening mode). In contrast, just above the threshold, H-NS dimers form 3-dimensional clusters, which are able to connect DNA sites that are distant from the genomic point of view (DNA-bridging mode). The model provides clear rationales for the experimental observations that the switch between the two modes is a threshold effect and that the ability of H-NS dimers to form higher order oligomers is crucial for their bridging capabilities.

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Cited by in corpus (6)

• Segregative phase separation scenario of the formation of the bacterial nucleoid
• Polymer compaction and bridging-induced clustering of protein-inspired patchy particles
• Preferential localization of the bacterial nucleoid
• Bacterial nucleoid: Interplay of DNA demixing and supercoiling
• Impact of self-association on the architectural properties of bacterial nucleoid proteins
• Requirements for DNA-bridging proteins to act as topological barriers of the bacterial genome