Nonspecifically bound proteins spin while diffusing along DNA.
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.
Blainey
Paul C
PC
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Luo
Guobin
G
Kou
S C
SC
Mangel
Walter F
WF
Verdine
Gregory L
GL
Bagchi
Biman
B
Xie
X Sunney
XS
D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D004058:Diffusion; D008956:Models, Chemical; D011485:Protein Binding
D004268:DNA-Binding Proteins; D004247:DNA