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Molecular and Cellular Biology, December 2009, p. 6232-6244, Vol. 29, No. 23
0270-7306/09/$08.00+0     doi:10.1128/MCB.00708-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Structural Basis of Alternative DNA Recognition by Maf Transcription Factors{triangledown}

Hirofumi Kurokawa,1,2* Hozumi Motohashi,2 Shinji Sueno,3 Momoko Kimura,2 Hiroaki Takagawa,3 Yousuke Kanno,3 Masayuki Yamamoto,2,{dagger} and Toshiyuki Tanaka3,{dagger}*

Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai 980-8577,1 Tohoku University Graduate School of Medicine, Sendai 980-8575,2 Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan3

Received 1 June 2009/ Returned for modification 11 July 2009/ Accepted 12 September 2009

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.


* Corresponding author. Mailing address for Hirofumi Kurokawa: Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan. Phone: 81-22-717-8085. Fax: 81-22-717-8090. E-mail: hkuro{at}m.tains.tohoku.ac.jp. Mailing address for Toshiyuki Tanaka: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan. Phone: 81-29-853-6706. Fax: 81-29-853-6706. E-mail: ttanaka{at}tara.tsukuba.ac.jp

{triangledown} Published ahead of print on 21 September 2009.

{dagger} M.Y. and T.T. contributed equally to this study.


Molecular and Cellular Biology, December 2009, p. 6232-6244, Vol. 29, No. 23
0270-7306/09/$08.00+0     doi:10.1128/MCB.00708-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.