Histone-like nucleoid-structuring protein

H-NS has a specific topology that allows it to condense bacterial DNA into a superhelical structure based on evidence from X-ray crystallography. H-NS also contains an unstructured linker region, also known as a Q-linker. The C-Terminal domain, also known as the DNA Binding Domain (DBD), shows high affinity for regions in DNA that are rich in Adenine and Thymine and present in a hook-like motif in a minor groove. The base stacking present in this AT rich region of the DNA allows for minor widening of the minor groove that is preferential for binding. Common DBD's include AACTA and TACTA regions which can appear hundreds of times throughout the genome. Within these AT-rich regions, the minor groove has a width of 3.5 Å, which is preferential for H-NS binding. In E. coli, it was observed that H-NS restructures the genome into microdomains in vivo. While the bacterial genome is split into four different macrodomains including Ori and Ter (macrodomain of E. coli and Shigella spp. in which H-NS is encoded), it is thought that H-NS plays a role in the formation of these small 10 kb microdomains throughout the genome. == Function ==

Expression control A major function of H-NS is to influence DNA topology (Figure 2). H-NS is responsible for formation of nucleofilaments along the DNA and DNA-DNA bridges. H-NS is known as a passive DNA bridger, meaning that it binds two distant segments of DNA and remains stationary, forming a loop. This DNA loop formation allows H-NS to control gene expression. The CTD binds to the bacterial DNA in such a way that inhibits the function of RNA polymerase. This is a common feature seen in horizontally acquired genes. Structural studies of H-NS use bacterial species such as E. coli and Shigella spp. because the C-Terminal Domain is completely conserved. The presence of magnesium ions (Mg2+) has been shown to allow H-NS to form a slightly open to completely open conformational change in structure that will ultimately alter the interaction between the negatively charged NTD and positively charged CTD. The charges seen in the NTD and CTD may explain how H-NS remains sensitive to changes in temperature and osmolarity (pH below 7.4). Other functions H-NS can also interact with other proteins and influence their function, for example it can interact with the flagellar motor protein FliG to increase its activity. == Clinical significance ==

s (ORF) of the specialized virulence plasmid in Shigella spp. is AT-rich, allowing for long term regulation of this plasmid by H-NS. Aforementioned, studies show that temperature sensitive H-NS will dissociate from bacterial DNA at 37 °C, triggering RNA polymerase to transcribe virF, the gene responsible for the expression of VirF. VirF is the main regulator of the virulence cascade and is expressed due to the temperature sensitive "hinge" region of the virF promoter changing conformation so that is no longer favorable for DNA-bridging by H-NS (Figure 3). Once VirF is expressed, it up regulates the production of icsA, functions to promote motility, and virB, encodes the next regulation protein in the Shigella cascade. As soon as VirB is expressed, it will disrupt H-NS for the rest of the virulence plasmid. Shigella spp. contain "molecular backups", or paralogues, to H-NS that have been studied in detail due to their apparent assistance in organization of the virulence plasmid. StpA is a paralogue of H-NS that is conserved across the species but the other, Sfh is expressed solely in the S. flexneri mutant strain 2457T. This mutant strain is of much interest to researchers because it acts as a replacement for H-NS since 2457T does not contain the hns gene. The correlation between H-NS and its paralogues is poorly understood at this time. Due to importance of these paralogues in the absence of H-NS in the mutant, further research and focus on these paralogues could lead to promising antibacterial treatments. == References ==