Localization of bound water in the solution structure of a complex of the erythroid transcription factor GATA-1 with DNA

Structure. 1994 Feb 15;2(2):89-94. doi: 10.1016/s0969-2126(00)00011-3.


Background: The erythroid specific transcription factor GATA-1 is responsible for the regulation of transcription of erythroid-expressed genes and is an essential component required for the generation of the erythroid lineage. GATA-1 binds specifically as a monomer to the asymmetric consensus target sequence (T/A)GATA-(A/G) found in the cis-regulatory elements of all globin genes and most other erythroid specific genes that have been examined. We have previously determined the solution structure of the complex of the zinc-containing DNA-binding domain of chicken GATA-1 with its cognate DNA target site by multidimensional heteronuclear NMR. From previous studies of complexes between proteins and DNA, water appears to play an important role in DNA-protein recognition by mediating bridging hydrogen bonds between functional groups on the protein and DNA bases. Solvation free energy calculations, however, suggest that hydrophobic interactions should exclude water from parts of the GATA-1:DNA interface.

Results: Using water-selective two-dimensional heteronuclear magnetic resonance spectroscopy, we have identified the location of bound water molecules in the specific complex of chicken GATA-1 with DNA. A number of water molecules could be detected between the protein and the phosphate backbone, as well as at the solvent exposed surface of the protein. However, no water molecules could be observed at the interface of the protein with the bases of the DNA. With only one exception, the bound water molecules have a residency time > 200-300 ps.

Conclusions: Unlike other protein-DNA complexes, the majority of specific interactions between GATA-1 and the DNA bases in the major groove are hydrophobic in nature. The exclusion of water from the protein-DNA base interface in the major groove supports the view that the specific binding energy is indeed dominated by hydrophobic effects.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Chickens
  • DNA / chemistry*
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Erythroid-Specific DNA-Binding Factors
  • Hydrogen Bonding
  • Magnetic Resonance Spectroscopy / methods
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Conformation
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism
  • Water


  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • Transcription Factors
  • Water
  • DNA