Search by proteins for their DNA target site: 1. The effect of DNA conformation on protein sliding.
Bottom Line: The search dynamics for DBPs on circular DNA is therefore markedly different compared with linear B-DNA.Our results suggest that, for a given DBP, the rotation-coupled sliding dynamics is precluded in highly curved DNA (as well as for over-twisted DNA) because of the large electrostatic energy barrier between the inside and outside of the DNA molecule.Under such circumstances, proteins prefer to hop in order to explore interior DNA sites.
Affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.Show MeSH
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Mentions: We addressed this question by estimating the number of positions probed by Sap-1 during the simulations using sliding dynamics (26). In addition, we measured D1 from the linear behavior of the mean square displacement along the DNA contour (see Materials and Methods section) of Sap-1 using only the sliding search mode or a combination of sliding and hopping. The results are presented in Figure 4 as a function of ΔW. For DNA with 0 ≤ ΔW < 1.8 Å (corresponds to circular DNA with 100 < Nbp ≤ 500; i.e. for minimally curved DNA structures), the number of visited sites shows a roughly constant value of 50–70. This means that Sap-1 scanned all these DNA molecules with roughly the same efficiency. However, in highly curved DNA minicircles, where ΔW ≥ 1.8 Å (Nbp ≤ 100), the number of probed positions decreases sharply because of a decrease in the use of sliding (Figure 3B), even though hopping-assisted diffusion (green line Figure 4B) increases along the DNA contour. Therefore, the optimal search efficiency was achieved for ΔW ∼ 2.1 Å (the curvature of the corresponding DNA is 0.02 per Å), where Sap-1 diffuses relatively fast (D1 = 4.43 Å2/time step) by hopping yet scanned ∼62 bp (out of 90) by sliding. When ΔW values are too small or large, which corresponds to very low or high curvatures, the result is either very fast diffusion without binding the DNA base pairs tightly (i.e. without sliding) or slow diffusion with repeated visits to the same DNA sites.
Affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.