Insights from modeling the 3D structure of DNA-CBF3b complex

A 3-dimensional model for a DNA-protein interaction has been developed. The protein component is the 61-residue fragment (res. 11-71) of subunit b of the yeast centromeric DNA binding factor 3, CBF3b. The CBF3b fragments bind to the 17 base pairs (5'-CGGAGGACTGTCCTCCG-3') as a symmetric homodimer, with each folded into three distinct conformations: a compact, zinc-binding domain (res. 11-44); an extended linker (res. 45-57); and an alpha-helical dimerization element (res. 58-71). The DNA fragment in the complex is featured by a relatively straight conformation with only slight deviation from a standard B-structure, and a large part of the major groove not blocked by the protein. The large DNA open area provides the necessary space for the other subunits of CBF3 to bind coordinately with CBF3b, fully consistent with the observation that the cooperation of all four CBF3 components is absolutely required to constitute an activity that specifically interacts with centromere DNA. The model also provides a footing for further considering the possible binding arrangements of the other three subunits, namely CBF3a, CBF3c, and CBF3d.