ELECTROSTATIC MECHANISM FOR DNA BENDING BY BZIP PROTEINS

Biology is replete with examples of protein-induced DNA bending, yet t he forces responsible for bending have been neither established nor qu antified. Mirzabekov and Rich proposed in 1979 that asymmetric neutral ization of the anionic phosphodiester backbone by basic histone protei ns could provide a thermodynamic driving force for DNA bending in the nucleosome core particle [Mirzabekov, A. D., gr Rich, A. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 1118-1121]. Strauss and Maher lent support to this proposal in 1994 by demonstrating that replacement of six pro ximal phosphate residues with neutral methylphosphonates resulted in D NA bent spontaneously toward the neutralized face [Strauss, J. K., gr Maher, L. J., III (1994) Science 266, 1829-1834; Strauss, J. K., Praka sh, T. P., Roberts, C., Switzer, C., & Maher, L. J., III (1996) Chem. Biol. 3, 671-678; Strauss, J. K., Roberts, C.; Nelson, M. G.; Switzer, C., Br Maher, J. L., III (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 951 5-9520]. Here it is shown that bZIP proteins bend DNA via a mechanism involving direct contacts between one or two basic side chains and a s ymmetry-related pair of unique, nonbridging phosphate oxygens. The loc ations of these phosphates provide direct experimental support for a p rotein-induced bending mechanism based on asymmetric charge neutraliza tion. This straightforward mechanism is compatible with many DNA-recog nition motifs and may represent a general strategy for the assembly of protein-DNA complexes of defined stereochemistries.