title: Search by proteins for their DNA target site: 1. The effect of DNA conformation on protein sliding.
abstract: The recognition of DNA-binding proteins (DBPs) to their specific site often precedes by a search technique in which proteins slide, hop along the DNA contour or perform inter-segment transfer and 3D diffusion to dissociate and re-associate to distant DNA sites. In this study, we demonstrated that the strength and nature of the non-specific electrostatic interactions, which govern the search dynamics of DBPs, are strongly correlated with the conformation of the DNA. We tuned two structural parameters, namely curvature and the extent of helical twisting in circular DNA. These two factors are mutually independent of each other and can modulate the electrostatic potential through changing the geometry of the circular DNA conformation. 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. 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.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Arnab
authors.initials: A
authors.lastname: Bhattacherjee
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel Koby.Levy@weizmann.ac.il.
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Levy
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004270:DNA, Circular / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D055672:Static Electricity
chemical_list: D004270:DNA, Circular; D004268:DNA-Binding Proteins; D004247:DNA