Limits...
Search by proteins for their DNA target site: 1. The effect of DNA conformation on protein sliding.

Bhattacherjee A, Levy Y - Nucleic Acids Res. (2014)

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.The change in the balance between sliding and hopping propensities as a function of DNA curvature or twisting may result in different search efficiency and speed.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.

Show MeSH
Role of DNA curvature in determining the efficiency of DNA search performed by Sap-1 at Cs = 0.02 M. (A) The efficiency is measured by the number of base pairs probed by Sap-1 using sliding dynamics during the simulation and presented as a function of the difference between the outer and inner major groove widths, ΔW (caused by changes in DNA curvature). (B) The one-dimensional diffusion coefficient D1 calculated for the portions of the simulation during which Sap-1 scanned the DNA contour via pure sliding (blue circles) and for the portions during which Sap-1 was bound to the DNA (green circles) by either the sliding or hopping modes of dynamics. As sliding frequency decreases sharply for ΔW ≥ 1.8 Å, D1 values were not calculated beyond this point. The extreme right point (close to ΔW = 4.0) is an outlier, which represents the results for a circular DNA with a circumference of 50 bp. The inner core of this DNA is smaller than the size of Sap-1, which forces Sap-1 to diffuse freely and prevents sliding and hopping interactions. Gray shaded region denotes DNA minicircles of circumference ≤ 100 bp.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4227778&req=5

Figure 4: Role of DNA curvature in determining the efficiency of DNA search performed by Sap-1 at Cs = 0.02 M. (A) The efficiency is measured by the number of base pairs probed by Sap-1 using sliding dynamics during the simulation and presented as a function of the difference between the outer and inner major groove widths, ΔW (caused by changes in DNA curvature). (B) The one-dimensional diffusion coefficient D1 calculated for the portions of the simulation during which Sap-1 scanned the DNA contour via pure sliding (blue circles) and for the portions during which Sap-1 was bound to the DNA (green circles) by either the sliding or hopping modes of dynamics. As sliding frequency decreases sharply for ΔW ≥ 1.8 Å, D1 values were not calculated beyond this point. The extreme right point (close to ΔW = 4.0) is an outlier, which represents the results for a circular DNA with a circumference of 50 bp. The inner core of this DNA is smaller than the size of Sap-1, which forces Sap-1 to diffuse freely and prevents sliding and hopping interactions. Gray shaded region denotes DNA minicircles of circumference ≤ 100 bp.

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.


Search by proteins for their DNA target site: 1. The effect of DNA conformation on protein sliding.

Bhattacherjee A, Levy Y - Nucleic Acids Res. (2014)

Role of DNA curvature in determining the efficiency of DNA search performed by Sap-1 at Cs = 0.02 M. (A) The efficiency is measured by the number of base pairs probed by Sap-1 using sliding dynamics during the simulation and presented as a function of the difference between the outer and inner major groove widths, ΔW (caused by changes in DNA curvature). (B) The one-dimensional diffusion coefficient D1 calculated for the portions of the simulation during which Sap-1 scanned the DNA contour via pure sliding (blue circles) and for the portions during which Sap-1 was bound to the DNA (green circles) by either the sliding or hopping modes of dynamics. As sliding frequency decreases sharply for ΔW ≥ 1.8 Å, D1 values were not calculated beyond this point. The extreme right point (close to ΔW = 4.0) is an outlier, which represents the results for a circular DNA with a circumference of 50 bp. The inner core of this DNA is smaller than the size of Sap-1, which forces Sap-1 to diffuse freely and prevents sliding and hopping interactions. Gray shaded region denotes DNA minicircles of circumference ≤ 100 bp.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4227778&req=5

Figure 4: Role of DNA curvature in determining the efficiency of DNA search performed by Sap-1 at Cs = 0.02 M. (A) The efficiency is measured by the number of base pairs probed by Sap-1 using sliding dynamics during the simulation and presented as a function of the difference between the outer and inner major groove widths, ΔW (caused by changes in DNA curvature). (B) The one-dimensional diffusion coefficient D1 calculated for the portions of the simulation during which Sap-1 scanned the DNA contour via pure sliding (blue circles) and for the portions during which Sap-1 was bound to the DNA (green circles) by either the sliding or hopping modes of dynamics. As sliding frequency decreases sharply for ΔW ≥ 1.8 Å, D1 values were not calculated beyond this point. The extreme right point (close to ΔW = 4.0) is an outlier, which represents the results for a circular DNA with a circumference of 50 bp. The inner core of this DNA is smaller than the size of Sap-1, which forces Sap-1 to diffuse freely and prevents sliding and hopping interactions. Gray shaded region denotes DNA minicircles of circumference ≤ 100 bp.
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.

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.The change in the balance between sliding and hopping propensities as a function of DNA curvature or twisting may result in different search efficiency and speed.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.

Show MeSH