Multiple-binding-site mechanism explains concentration-dependent unbinding rates of DNA-binding proteins

Charles E. Sing, Monica Olvera De La Cruz, John F. Marko

Research output: Contribution to journalArticlepeer-review


Recent work has demonstrated concentrationdependent unbinding rates of proteins from DNA, using fluorescence visualization of the bacterial nucleoid protein Fis [Graham et al. (2011) (Concentration-dependent exchange accelerates turnover of proteins bound to double-stranded DNA. Nucleic Acids Res., 39:2249)]. The physical origin of this concentration-dependence is unexplained. We use a combination of coarse-grained simulation and theory to demonstrate that this behavior can be explained by taking into account the dimeric nature of the protein, which permits partial dissociation and exchange with other proteins in solution. Concentration-dependent unbinding is generated by this simple model, quantitatively explaining experimental data. This effect is likely to play a major role in determining binding lifetimes of proteins in vivo where there are very high concentrations of solvated molecules.

Original languageEnglish (US)
Pages (from-to)3783-3791
Number of pages9
JournalNucleic acids research
Issue number6
StatePublished - Apr 2014
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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