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Histone-like nucleoid-structuring protein

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H-NS
Solution structure of the N-terminal domain (oligomerization domain) of the bacterial chromatin-structuring protein h-ns
Identifiers
SymbolH-NS
PfamPF00816
InterProIPR001801
CATH[ P0ACF8]
SCOP21hns / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Histone-like nucleoid-structuring protein (H-NS), is one of twelve nucleoid-associated proteins (NAPs)[1] whose main function is the organization of genetic material, including the regulation of gene expression via xenogeneic silencing.[2] H-NS is characterized by an N-terminal domain (NTD) consisting of two dimerization sites, a linker region that is unstructured and a C-terminal domain (CTD) that is responsible for DNA-binding.[2] This protein provides essential nucleoid compaction and regulation of genes, mainly silencing.[2] At specific cell conditions, such as change in temperature, H-NS can be dissociated from the DNA duplex, allowing for transcription by RNA polymerase, and in specific regions lead to pathogenic cascades.[3]

Structure

Gene repression by H-NS is caused by the formation of oligomers. These oligomers form due to dimerization of two sites in the N-terminal domain.[4]

Figure 1: The C-terminal domain (CTD) is also known as the DNA-binding domain. H-NS NTD's oligomerize with each other while the CTD binds to specific regions of DNA containing a specific topology called a TpA step.[5] Aromatic amino acid residues are labelled in gray, negatively charged particles are displayed in red, and positively charged particles are labelled in teal. H-bond lengths are displayed in magenta.
Figure 3: This figure portrays the oligomerization occuring in the alpha helices of the NTD in H-NS (and homologues) forming what is known as a "handshake topology" and an estimated view of how the CTD binds to DNA.


Function

Figure 2: The main differences between eukaryotic and bacterial mechanisms for organizing genetic material. (A) DNA (gray) that is bound to H-NS is organized into plectonemic supercoils and causes bridges in DNA duplexes. (B) Eukaryotic histones form toroidal supercoils and function by wrapping DNA around the octamers. [6]

A major function of H-NS is to influence DNA topology. H-NS is responsible for formation of nucleofilaments along the DNA and DNA-DNA bridges (refer to Figure 2). 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.[7] Relief of suppression by H-NS can be achieved by the binding of another protein, or by changes in DNA topology which can occur due to changes in temperature and osmolarity, for example.[8]

The C-Terminal Domain of H-NS 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.[7][9] 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.[7] This is a common feature seen in horizontally acquired genes.[10]

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.[11]

Clinical Significance

H-NS has a conserved role in the pathogenicity of gram-negative bacteria including Shigella spp. and Escherichia coli. It is implicated in the transcription of the virF gene leading to bacillary dysentery, a disease affecting children mainly seen in developing countries. These two bacterial species contain a virulence plasmid that is responsible for invasion of host cells and is regulated by H-NS.[12]

References

  1. ^ Winardhi RS, Yan J, Kenney LJ (October 2015). "H-NS Regulates Gene Expression and Compacts the Nucleoid: Insights from Single-Molecule Experiments". Biophysical Journal. 109 (7): 1321–1329. doi:10.1016/j.bpj.2015.08.016. PMC 4601063. PMID 26445432.
  2. ^ a b c Qin L, Erkelens AM, Ben Bdira F, Dame RT (December 2019). "The architects of bacterial DNA bridges: a structurally and functionally conserved family of proteins". Open Biology. 9 (12): 190223. doi:10.1098/rsob.190223. PMC 6936261. PMID 31795918.
  3. ^ Picker MA, Wing HJ (December 2016). "H-NS, Its Family Members and Their Regulation of Virulence Genes in Shigella Species". Genes. 7 (12): 112. doi:10.3390/genes7120112. PMC 5192488. PMID 27916940.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ Qin L, Erkelens AM, Ben Bdira F, Dame RT (December 2019). "The architects of bacterial DNA bridges: a structurally and functionally conserved family of proteins". Open Biology. 9 (12): 190223. doi:10.1098/rsob.190223. PMC 6936261. PMID 31795918.
  5. ^ Qin L, Erkelens AM, Ben Bdira F, Dame RT (December 2019). "The architects of bacterial DNA bridges: a structurally and functionally conserved family of proteins". Open Biology. 9 (12): 190223. doi:10.1098/rsob.190223. PMC 6936261. PMID 31795918.
  6. ^ Verma SC, Qian Z, Adhya SL (December 2019). "Architecture of the Escherichia coli nucleoid". PLoS Genetics. 15 (12): e1008456. doi:10.1371/journal.pgen.1008456. PMC 6907758. PMID 31830036.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  7. ^ a b c Qin L, Erkelens AM, Ben Bdira F, Dame RT (December 2019). "The architects of bacterial DNA bridges: a structurally and functionally conserved family of proteins". Open Biology. 9 (12): 190223. doi:10.1098/rsob.190223. PMC 6936261. PMID 31795918.
  8. ^ Dorman CJ (May 2004). "H-NS: a universal regulator for a dynamic genome". Nature Reviews. Microbiology. 2 (5): 391–400. doi:10.1038/nrmicro883. PMID 15100692.
  9. ^ Verma SC, Qian Z, Adhya SL (December 2019). "Architecture of the Escherichia coli nucleoid". PLoS Genetics. 15 (12): e1008456. doi:10.1371/journal.pgen.1008456. PMC 6907758. PMID 31830036.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ Lucchini S, Rowley G, Goldberg MD, Hurd D, Harrison M, Hinton JC (August 2006). "H-NS mediates the silencing of laterally acquired genes in bacteria". PLoS Pathogens. 2 (8): e81. doi:10.1371/journal.ppat.0020081. PMC 1550270. PMID 16933988.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  11. ^ Donato GM, Kawula TH (September 1998). "Enhanced binding of altered H-NS protein to flagellar rotor protein FliG causes increased flagellar rotational speed and hypermotility in Escherichia coli". The Journal of Biological Chemistry. 273 (37): 24030–24036. doi:10.1074/jbc.273.37.24030. PMID 9727020.
  12. ^ Picker MA, Wing HJ (December 2016). "H-NS, Its Family Members and Their Regulation of Virulence Genes in Shigella Species". Genes. 7 (12): E112. doi:10.3390/genes7120112. PMC 5192488. PMID 27916940.{{cite journal}}: CS1 maint: unflagged free DOI (link)
This article incorporates text from the public domain Pfam and InterPro: IPR001801
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