Browsing by Subject "Transcription machinery"

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    Facilitated dissociation of nucleoid-associated proteins from DNA in the bacterial confinement
    (Biophysical Society, 2022-04-05) Koşar, Zafer; Attar, A. Göktuğ; Erbaş, Aykut
    Transcription machinery depends on the temporal formation of protein-DNA complexes. Recent experiments demonstrated that not only the formation but also the lifetime of such complexes can affect the transcriptional machinery. In parallel, in vitro single-molecule studies showed that nucleoid-associated proteins (NAPs) leave the DNA rapidly as the bulk concentration of the protein increases via facilitated dissociation (FD). Nevertheless, whether such a concentration-dependent mechanism is functional in a bacterial cell, in which NAP levels and the 3d chromosomal structure are often coupled, is not clear a priori. Here, by using extensive coarse-grained molecular simulations, we model the unbinding of specific and nonspecific dimeric NAPs from a high-molecular-weight circular DNA molecule in a cylindrical structure mimicking the cellular confinement of a bacterial chromosome. Our simulations confirm that physiologically relevant peak protein levels (tens of micromolar) lead to highly compact chromosomal structures. This compaction results in rapid off rates (shorter DNA residence times) for specifically DNA-binding NAPs, such as the factor for inversion stimulation, which mostly dissociate via a segmental jump mechanism. Contrarily, for nonspecific NAPs, which are more prone to leave their binding sites via 1d sliding, the off rates decrease as the protein levels increase. The simulations with restrained chromosome models reveal that chromosome compaction is in favor of faster dissociation but only for specific proteins, and nonspecific proteins are not affected by the chromosome compaction. Overall, our results suggest that the cellular concentration level of a structural DNA-binding protein can be highly intermingled with its DNA residence time.