4EOT

Crystal structure of the MafA homodimer bound to the consensus MARE

4EOT の概要

• エントリーDOI: 10.2210/pdb4eot/pdb
• 分子名称: Transcription factor MafA, 5'-D(*CP*CP*GP*GP*TP*GP*CP*TP*GP*AP*GP*TP*CP*AP*GP*CP*AP*GP*G)-3', 5'-D(*CP*CP*CP*TP*GP*CP*TP*GP*AP*CP*TP*CP*AP*GP*CP*AP*CP*CP*G)-3', ... (5 entities in total)
• 機能のキーワード: leucine zipper, transcription factor, dna binding, nucleus, transcription-dna complex, transcription/dna
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q8NHW3
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 34808.16

構造登録者

Lu, X.,Guanga, G.,Wan, C.,Rose, R.B. (登録日: 2012-04-15, 公開日: 2012-11-28, 最終更新日: 2023-09-13)

主引用文献

Lu, X.,Guanga, G.P.,Wan, C.,Rose, R.B.
A Novel DNA Binding Mechanism for maf Basic Region-Leucine Zipper Factors Inferred from a MafA-DNA Complex Structure and Binding Specificities.
Biochemistry, 51:9706-9717, 2012

PubMed Abstract: MafA is a proto-oncoprotein and is critical for insulin gene expression in pancreatic β-cells. Maf proteins belong to the AP1 superfamily of basic region-leucine zipper (bZIP) transcription factors. Residues in the basic helix and an ancillary N-terminal domain, the Extended Homology Region (EHR), endow maf proteins with unique DNA binding properties: binding a 13 bp consensus site consisting of a core AP1 site (TGACTCA) flanked by TGC sequences and binding DNA stably as monomers. To further characterize maf DNA binding, we determined the structure of a MafA-DNA complex. MafA forms base-specific hydrogen bonds with the flanking G(-5)C(-4) and central C(0)/G(0) bases, but not with the core-TGA bases. However, in vitro binding studies utilizing a pulse-chase electrophoretic mobility shift assay protocol revealed that mutating either the core-TGA or flanking-TGC bases dramatically increases the binding off rate. Comparing the known maf structures, we propose that DNA binding specificity results from positioning the basic helix through unique phosphate contacts. The EHR does not contact DNA directly but stabilizes DNA binding by contacting the basic helix. Collectively, these results suggest a novel multistep DNA binding process involving a conformational change from contacting the core-TGA to contacting the flanking-TGC bases.

PubMed: 23148532
DOI: 10.1021/bi301248j

実験手法

X-RAY DIFFRACTION (2.855 Å)