Figure 6
MD simulations of sequential steps during TRF2-mediated DNA compaction.
(a) The TRF2 model used in MD simulations. Yellow: the specific DNA binding domain. White: the protein dimerization domain. Red: the nonspecific, positively charged DNA binding domain. (b) Protein dimerization: TRF2 dimerizes on DNA facilitated by 1-D diffusion on DNA. (c) DNA cross-over: random fluctuation of DNA leads to the initial contact between two DNA strands. (d) DNA zipping up: TRF2 molecules accumulate in the vicinity of the DNA-DNA contact leading to the alignment of DNA strands due to the fluctuation-driven “bridging-induced attraction” mechanism. (e) Additional folding of DNA: electrostatic screening by proteins allows close contact of three DNA strands. (f) Globule structure formation: additional folding of DNA in the protein-DNA complex. Protein molecules are modeled as rigid bodies that cannot bind DNA strands between protein subdomains. It is possible that parts of DNA with direct protein contact in MD simulations would be shielded from the DREEM imaging mechanism by actual TRF2 proteins and only protruding DNA loops or DNA folded at the edge of the globule structure are detected in DREEM images (Fig. 4b).
