title: Nonspecifically bound proteins spin while diffusing along DNA.
abstract: It is known that DNA-binding proteins can slide along the DNA helix while searching for specific binding sites, but their path of motion remains obscure. Do these proteins undergo simple one-dimensional (1D) translational diffusion, or do they rotate to maintain a specific orientation with respect to the DNA helix? We measured 1D diffusion constants as a function of protein size while maintaining the DNA-protein interface. Using bootstrap analysis of single-molecule diffusion data, we compared the results to theoretical predictions for pure translational motion and rotation-coupled sliding along the DNA. The data indicate that DNA-binding proteins undergo rotation-coupled sliding along the DNA helix and can be described by a model of diffusion along the DNA helix on a rugged free-energy landscape. A similar analysis including the 1D diffusion constants of eight proteins of varying size shows that rotation-coupled sliding is a general phenomenon. The average free-energy barrier for sliding along the DNA was 1.1 +/- 0.2 k(B)T. Such small barriers facilitate rapid search for binding sites.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Blainey
authors.forename: Guobin
authors.initials: G
authors.lastname: Luo
authors.forename: S C
authors.initials: SC
authors.lastname: Kou
authors.forename: Walter F
authors.initials: WF
authors.lastname: Mangel
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Verdine
authors.forename: Biman
authors.initials: B
authors.lastname: Bagchi
authors.forename: X Sunney
authors.initials: XS
authors.lastname: Xie
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D004058:Diffusion; D008956:Models, Chemical; D011485:Protein Binding
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA