Role of Internal DNA Motion on the Mobility of a Nucleoid-Associated Protein

Protein transport on DNA is at the core of the machinery of life. Here we investigated the influence of DNA internal motion on the mobility of Hfq, which is involved in several aspects of nucleic acid metabolism and is one of the nucleoid-associated proteins that shape the bacterial chromosome. Fluorescence microscopy was used to follow Hfq on double-stranded DNA that was stretched by confinement to a channel with a diameter of 125 nm. The protein mobility shows a strong dependence on the internal motion of DNA in that slower motion results in faster protein diffusion. A model of released diffusion is proposed that is based on three-dimensional diffusion through the interior of the DNA coil interspersed by periods in which the protein is immobilized in a bound state. We surmise that the coupling between DNA internal motion and protein mobility has important implications for DNA metabolism and protein-binding-related regulation of gene expression.