Electrostatic mechanism for DNA bending by bZIP proteins.
Biology is replete with examples of protein-induced DNA bending, yet the forces responsible for bending have been neither established nor quantified. Mirzabekov and Rich proposed in 1979 that asymmetric neutralization of the anionic phosphodiester backbone by basic histone proteins could provide a thermodynamic driving force for DNA bending in the nucleosome core particle [Mirzabekov, A. D., & 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 proximal phosphate residues with neutral methylphosphonates resulted in DNA bent spontaneously toward the neutralized face [Strauss, J. K., & Maher, L. J., III (1994) Science 266, 1829-1834; Strauss, J. K., Prakash, 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., & Maher, J. L., III (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 9515-9520]. Here it is shown that bZIP proteins bend DNA via a mechanism involving direct contacts between one or two basic side chains and a symmetry-related pair of unique, nonbridging phosphate oxygens. The locations of these phosphates provide direct experimental support for a protein-induced bending mechanism based on asymmetric charge neutralization. This straightforward mechanism is compatible with many DNA-recognition motifs and may represent a general strategy for the assembly of protein-DNA complexes of defined stereochemistries.
Paolella
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DN
Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA.
Liu
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Y
Fabian
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MA
Schepartz
A
A
D000595:Amino Acid Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D051790:G-Box Binding Factors; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D055672:Static Electricity; D013237:Stereoisomerism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D050976:Basic-Leucine Zipper Transcription Factors; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051790:G-Box Binding Factors; D014157:Transcription Factors; D004247:DNA