Structural analysis of MED-1 reveals unexpected diversity in the mechanism of DNA recognition by GATA-type zinc finger domains

Structural analysis of MED-1 reveals unexpected diversity in the mechanism of DNA recognition by GATA-type zinc finger domains. Lowry, J., Gamsjaeger, R., Thong, S., Hung, W., Kwan, A., Broitman-Maduro, G., Matthews, J., Maduro, M., & Mackay, J. Journal of Biological Chemistry, 284(9):5827-5835, 2009. cited By 17

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MED-1 is a member of a group of divergent GATA-type zinc finger proteins recently identified in several species of Caenorhabditis. The med genes are transcriptional regulators that are involved in the specification of the mesoderm and endoderm precursor cells in nematodes. Unlike other GATA-type zinc fingers that recognize the consensus sequence (A/C/ T)GATA(A/G), the MED-1 zinc finger (MED1zf) binds the larger and atypical site GTATACT(T/C)3. We have examined the basis for this unusual DNA specificity using a range of biochemical and biophysical approaches. Most strikingly, we show that although the core of the MED1zf structure is similar to that of GATA-1, the basic tail C-terminal to the zinc finger unexpectedly adopts an α-helical structure upon binding DNA. This additional helix appears to contact the major groove of the DNA, making contacts that explain the extended DNA consensus sequence observed for MED1zf. Our data expand the versatility of DNA recognition by GATA-type zinc fingers and perhaps shed new light on the DNA-binding properties of mammalian GATA factors. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

@ARTICLE{Lowry20095827,
author={Lowry, J.A. and Gamsjaeger, R. and Thong, S.Y. and Hung, W. and Kwan, A.H. and Broitman-Maduro, G. and Matthews, J.M. and Maduro, M. and Mackay, J.P.},
title={Structural analysis of MED-1 reveals unexpected diversity in the mechanism of DNA recognition by GATA-type zinc finger domains},
journal={Journal of Biological Chemistry},
year={2009},
volume={284},
number={9},
pages={5827-5835},
doi={10.1074/jbc.M808712200},
note={cited By 17},
url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-65549120319&doi=10.1074%2fjbc.M808712200&partnerID=40&md5=8c2a9f192f52f609c7e6a55967f01cb8},
affiliation={School of Molecular and Microbial Biosciences, University of Sydney, Sydney, NSW 2006, Australia; Department of Biology, University of California, Riverside, CA 92521, United States},
abstract={MED-1 is a member of a group of divergent GATA-type zinc finger proteins recently identified in several species of Caenorhabditis. The med genes are transcriptional regulators that are involved in the specification of the mesoderm and endoderm precursor cells in nematodes. Unlike other GATA-type zinc fingers that recognize the consensus sequence (A/C/ T)GATA(A/G), the MED-1 zinc finger (MED1zf) binds the larger and atypical site GTATACT(T/C)3. We have examined the basis for this unusual DNA specificity using a range of biochemical and biophysical approaches. Most strikingly, we show that although the core of the MED1zf structure is similar to that of GATA-1, the basic tail C-terminal to the zinc finger unexpectedly adopts an α-helical structure upon binding DNA. This additional helix appears to contact the major groove of the DNA, making contacts that explain the extended DNA consensus sequence observed for MED1zf. Our data expand the versatility of DNA recognition by GATA-type zinc fingers and perhaps shed new light on the DNA-binding properties of mammalian GATA factors. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.},
keywords={Caenorhabditis;  Consensus sequence;  DNA consensus sequence;  DNA recognition;  DNA-binding properties;  Helical structures;  Precursor cells;  Transcriptional regulator;  Zinc finger;  Zinc finger domains;  Zinc finger protein, Binding energy;  DNA;  Mammals;  Nucleic acids;  Structural analysis;  Zinc, Genes, palindromic DNA;  transcription factor GATA;  transcription factor MED 1;  unclassified drug;  zinc finger protein;  Caenorhabditis elegans protein;  DNA;  MED 1 protein, C elegans;  MED-1 protein, C elegans;  primer DNA;  transcription factor GATA 1;  zinc finger protein, alpha helix;  article;  binding affinity;  carboxy terminal sequence;  consensus sequence;  molecular recognition;  nonhuman;  priority journal;  protein DNA binding;  protein domain;  protein expression;  protein function;  protein structure;  structure analysis;  amino acid sequence;  animal;  calorimetry;  chemistry;  gel mobility shift assay;  genetics;  metabolism;  molecular genetics;  nuclear magnetic resonance spectroscopy;  sequence homology;  site directed mutagenesis;  surface plasmon resonance, Caenorhabditis;  Mammalia;  Nematoda, Amino Acid Sequence;  Animals;  Caenorhabditis elegans Proteins;  Calorimetry;  DNA;  DNA Primers;  Electrophoretic Mobility Shift Assay;  GATA Transcription Factors;  GATA1 Transcription Factor;  Magnetic Resonance Spectroscopy;  Molecular Sequence Data;  Mutagenesis, Site-Directed;  Sequence Homology, Amino Acid;  Surface Plasmon Resonance;  Zinc Fingers},
correspondence_address1={Mackay, J.P.; School of Molecular and Microbial Biosciences, , Sydney, NSW 2006, Australia; email: j.mackay@usyd.edu.au},
issn={00219258},
coden={JBCHA},
pubmed_id={19095651},
language={English},
abbrev_source_title={J. Biol. Chem.},
document_type={Article},
source={Scopus},
}

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