title: Predicting the effect of ions on the conformation of the H-NS dimerization domain.
abstract: The histone-like nucleoid structuring protein (H-NS) is a DNA-organizing protein in bacteria. It contains a DNA-binding domain and a dimerization domain, connected by a flexible linker region. Dimerization occurs through the formation of a helical bundle, including a coiled-coil interaction motif. Two conformations have been resolved, for different sequences of Escherichia coli H-NS, resulting in an antiparallel coiled-coil for the shorter wild-type sequence, and a parallel coiled-coil for the longer C21S mutant. Because H-NS functions as a thermo- and osmosensor, these conformations may both be functionally relevant. Molecular simulation can complement experiments by modeling the dynamical time evolution of biomolecular systems in atomistic detail. We performed a molecular-dynamics study of the H-NS dimerization domain, showing that the parallel complex is sensitive to changes in salt conditions: it is unstable in absence of NaCl, but stable at physiological salt concentrations. In contrast, the stability of the antiparallel complex is not salt-dependent. The stability of the parallel complex also appears to be affected by mutation of the critical but nonconserved cysteine residue at position 21, whereas the antiparallel complex is not. Together, our simulations suggest that osmoregulation could be mediated by changes in the ratio of parallel- and antiparallel-oriented H-NS dimers.
authors: Computational Chemistry, van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam, The Netherlands. j.vreede@uva.nl
authors: Jocelyne
authors: J
authors: Vreede
authors: Remus Th
authors: RT
authors: Dame
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D036781:Fimbriae Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry*; D012486:Salmonella typhimurium / Q000737:chemistry; D012965:Sodium Chloride
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C529458:FimG protein, E coli; C031908:H-NS protein, bacteria; D021122:Protein Subunits; D036781:Fimbriae Proteins; D012965:Sodium Chloride