Structural Basis of Alternative DNA Recognition by Maf Transcription Factors

ABSTRACT Maf transcription factors constitute a family of the basic region-leucine zipper (bZip) factors and recognize unusually long DNA motifs (13 or 14 bp), termed the Maf recognition element (MARE). The MARE harbors extended GC sequences on each side of its core motif, which is similar to TRE or CRE (7 or 8 bp) recognized by the AP1 and CREB/ATF families, respectively. To ascertain the structural basis governing the acquirement of such unique DNA recognition, we determined the crystal structure of the MafG-DNA complex. Each MafG monomer consists of three helices in which the carboxyl-terminal long helix organizes one DNA-contacting element and one coiled-coil dimer formation element. To our surprise, two well-conserved residues, Arg57 and Asn61 in the basic region, play critical roles in Maf-specific DNA recognition. These two residues show unique side-chain orientations and interact directly with the extended GC bases. Maf-specific residues in the amino-terminal and basic regions appear to indirectly stabilize MARE recognition through DNA backbone phosphate interactions. This study revealed an alternative DNA recognition mechanism of the bZip factors that bestows specific target gene profiles upon Maf homodimers or Maf-containing heterodimers.

[1]  T. Rushmore,et al.  The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. , 1991, The Journal of biological chemistry.

[2]  Ken Itoh,et al.  Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins , 1994, Nature.

[3]  P. Kraulis.  A program to produce both detailed and schematic plots of protein structures , 1991 .

[4]  T. Rosenberg,et al.  Novel MAF mutation in a family with congenital cataract-microcornea syndrome. , 2007, Molecular vision.

[5]  Makoto Kobayashi,et al.  MafT, a new member of the small Maf protein family in zebrafish. , 2004, Biochemical and biophysical research communications.

[6]  Masayuki Yamamoto,et al.  Nrf2-Keap1 defines a physiologically important stress response mechanism. , 2004, Trends in molecular medicine.

[7]  D E McRee,et al.  XtalView/Xfit--A versatile program for manipulating atomic coordinates and electron density. , 1999, Journal of structural biology.

[8]  H. Ogino,et al.  Induction of lens differentiation by activation of a bZIP transcription factor, L-Maf. , 1998, Science.

[9]  Z. Otwinowski,et al.  Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[10]  K. Kataoka,et al.  Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor , 1995, Molecular and cellular biology.

[11]  D. Zack,et al.  A mutation in NRL is associated with autosomal dominant retinitis pigmentosa , 1999, Nature Genetics.

[12]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[13]  K. Igarashi,et al.  The heme-Bach1 pathway in the regulation of oxidative stress response and erythroid differentiation. , 2006, Antioxidants & redox signaling.

[14]  A. Grinberg,et al.  DNA sequence‐dependent folding determines the divergence in binding specificities between Maf and other bZIP proteins , 2001, The EMBO journal.

[15]  J. N. Mark Glover,et al.  Crystal structure of the heterodimeric bZIP transcription factor c-Fos–c-Jun bound to DNA , 1995, Nature.

[16]  B. Matthews,et al.  A new DNA-binding motif in the Skn-1 binding domain–DNA complex , 1998, Nature Structural Biology.

[17]  K. Kataoka,et al.  Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms heterodimers with both Fos and Jun , 1994, Molecular and cellular biology.

[18]  J. D. Engel,et al.  Predictive base substitution rules that determine the binding and transcriptional specificity of Maf recognition elements , 2006, Genes to cells : devoted to molecular & cellular mechanisms.

[19]  L. McIntosh,et al.  Inhibitory Module of Ets-1 Allosterically Regulates DNA Binding through a Dipole-facilitated Phosphate Contact* , 2002, The Journal of Biological Chemistry.

[20]  K. Kataoka,et al.  v-maf, a viral oncogene that encodes a "leucine zipper" motif. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. Burch,et al.  DNA-binding specificity of the PAR basic leucine zipper protein VBP partially overlaps those of the C/EBP and CREB/ATF families and is influenced by domains that flank the core basic region , 1995, Molecular and cellular biology.

[22]  Tsutomu Ohta,et al.  Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. , 2006, Molecular cell.

[23]  W. Delano.  The PyMOL Molecular Graphics System , 2002 .

[24]  James Douglas Engel,et al.  Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors. , 2002, Gene.

[25]  T. Nagai,et al.  Regulation of NF-E2 Activity in Erythroleukemia Cell Differentiation* , 1998, The Journal of Biological Chemistry.

[26]  K. Struhl,et al.  The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted α Helices: Crystal structure of the protein-DNA complex , 1992, Cell.

[27]  Masayuki Yamamoto,et al.  Solution structure of the DNA-binding domain of MafG , 2002, Nature Structural Biology.

[28]  George M Sheldrick,et al.  Substructure solution with SHELXD. , 2002, Acta crystallographica. Section D, Biological crystallography.

[29]  Toshio Hakoshima,et al.  Structural basis for the diversity of DNA recognition by bZIP transcription factors , 2000, Nature Structural Biology.

[30]  J. D. Engel,et al.  Evaluation of MafG interaction with Maf recognition element arrays by surface plasmon resonance imaging technique , 2004, Genes to cells : devoted to molecular & cellular mechanisms.

[31]  D. Zack,et al.  The basic motif-leucine zipper transcription factor Nrl can positively regulate rhodopsin gene expression. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Lyon,et al.  A dominant mutation within the DNA-binding domain of the bZIP transcription factor Maf causes murine cataract and results in selective alteration in DNA binding. , 2003, Human molecular genetics.

[33]  K. Kataoka,et al.  MafA Is a Glucose-regulated and Pancreatic β-Cell-specific Transcriptional Activator for the Insulin Gene* , 2002, The Journal of Biological Chemistry.

[34]  T. Richmond,et al.  The X-ray structure of the GCN4-bZIP bound to ATF/CREB site DNA shows the complex depends on DNA flexibility. , 1993, Journal of molecular biology.

[35]  T. Curran,et al.  A conserved region adjacent to the basic domain is required for recognition of an extended DNA binding site by Maf/Nrl family proteins. , 1994, Oncogene.

[36]  D. Ray,et al.  A heterozygous c-Maf transactivation domain mutation causes congenital cataract and enhances target gene activation. , 2007, Human molecular genetics.

[37]  L. Staudt,et al.  Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma. , 2004, Cancer cell.

[38]  K. Itoh,et al.  An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. , 1997, Biochemical and biophysical research communications.

[39]  A. Jackson,et al.  A conserved retina-specific gene encodes a basic motif/leucine zipper domain. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[40]  J. Thornton,et al.  NUCPLOT: a program to generate schematic diagrams of protein-nucleic acid interactions. , 1997, Nucleic acids research.

[41]  J. D. Engel,et al.  Positive or Negative MARE-Dependent Transcriptional Regulation Is Determined by the Abundance of Small Maf Proteins , 2000, Cell.

[42]  S. Hirohashi,et al.  Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. , 2008, Cancer research.

[43]  A. Nienhuis,et al.  Inducibility of the HS II enhancer depends on binding of an erythroid specific nuclear protein. , 1990, Nucleic acids research.