4.8 Article

The phage T4 MotA transcription factor contains a novel DNA binding motif that specifically recognizes modified DNA

Journal

NUCLEIC ACIDS RESEARCH
Volume 46, Issue 10, Pages 5308-5318

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gky292

Keywords

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Funding

  1. National Institutes of Health (NIH) [GM066934]
  2. Cancer Center core grant [CA21765]
  3. American Lebanese Syrian Associated Charities (ALSAC)
  4. Intramural Research Program of the National Institutes of Health, NIDDK
  5. U.S. Department of Energy [W-31-109-Eng-38]
  6. St Jude Children's Research Hospital

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During infection, bacteriophage T4 produces the MotA transcription factor that redirects the host RNA polymerase to the expression of T4 middle genes. The C-terminal 'double-wing' domain of MotA binds specifically to the MotA box motif of middle T4 promoters. We report the crystal structure of this complex, which reveals a new mode of protein-DNA interaction. The domain binds DNA mostly via interactions with the DNA backbone, but the binding is enhanced in the specific cognate structure by additional interactions with the MotA box motif in both the major and minor grooves. The linker connecting the two MotA domains plays a key role in stabilizing the complex via minor groove interactions. The structure is consistent with our previous model derived from chemical cleavage experiments using the entire transcription complex. alpha- and beta-D-glucosyl-5-hydroxymethyl-deoxycytosine replace cytosine in T4 DNA, and docking simulations indicate that a cavity in the cognate structure can accommodate the modified cytosine. Binding studies confirm that the modification significantly enhances the binding affinity of MotA for the DNA. Consequently, our work reveals how a DNA modification can extend the uniqueness of small DNA motifs to facilitate the specificity of protein-DNA interactions.

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