Structural Basis of Alternative DNA Recognition by Maf Transcription Factors
Structural Basis of Alternative DNA Recognition by Maf Transcription Factors
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DOI：
10.1128/mcb.00708-09
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发表时间：
2009-12-01
影响因子：
5.3
通讯作者：
Tanaka, Toshiyuki
中科院分区：
文献类型：
--
作者：
Kurokawa, Hirofumi;Motohashi, Hozumi;Tanaka, Toshiyuki
MAF转录因子是一个基本的区域亮氨酸拉链(BZip)转录因子家族，可以识别非常长的DNA基序(13或14个碱基)，称为MAF识别元件(MAF Recognition Element，MARE)。母马在其核心基序的两侧都含有扩展的GC序列，这与AP1和CREB/ATF家族分别识别的TrE或Cre(7或8bp)相似。为了确定控制这种独特DNA识别的结构基础，我们测定了MafG-DNA复合体的晶体结构。每个MafG单体由三个螺旋组成，其中羧基末端的长螺旋由一个DNA接触元件和一个盘绕二聚体形成元件组成。令我们惊讶的是，两个保守的残基，碱性区域的Arg57和Asn61，在Maf特异性DNA识别中发挥着关键作用。这两个残基显示出独特的侧链取向，并直接与扩展的GC碱基相互作用。MAF在氨基末端和碱性区域的特定残基似乎通过DNA骨架磷酸相互作用间接稳定了MARE的识别。这项研究揭示了bZip因子的另一种DNA识别机制，即赋予MAF同源二聚体或含有MAF的异源二聚体特定的靶基因图谱。
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.