1OZJ

Crystal structure of Smad3-MH1 bound to DNA at 2.4 A resolution

1OZJ の概要

• エントリーDOI: 10.2210/pdb1ozj/pdb
• 関連するPDBエントリー: 1mhd
• 分子名称: Smad binding element, SMAD 3, ZINC ION, ... (5 entities in total)
• 機能のキーワード: smad, mad homology domain 1, dna recognition, tgf-beta signaling, zinc-binding module, transcription-dna complex, transcription/dna
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P84022
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 43003.40

構造登録者

Chai, J.,Wu, J.-W.,Yan, N.,Massague, J.,Pavletich, N.P.,Shi, Y. (登録日: 2003-04-09, 公開日: 2004-03-23, 最終更新日: 2024-02-14)

主引用文献

Chai, J.,Wu, J.-W.,Yan, N.,Massague, J.,Pavletich, N.P.,Shi, Y.
Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA binding.
J.Biol.Chem., 278:20327-20331, 2003

PubMed Abstract: The Smad family of proteins mediates transforming growth factor-beta signaling from cell membrane to the nucleus. In the nucleus, Smads serve as transcription factors by directly binding to specific DNA sequences and regulating the expression of ligand-response genes. A previous structural analysis, at 2.8-A resolution, revealed a novel DNA-binding mode for the Smad MH1 domain but did not allow accurate assignment of the fines features of protein-DNA interactions. The crystal structure of a Smad3 MH1 domain bound to a palindromic DNA sequence, determined at 2.4-A resolution, reveals a surprisingly important role for water molecules. The asymmetric placement of the DNA-binding motif (a conserved 11-residue beta-hairpin) in the major groove of DNA is buttressed by seven well ordered water molecules. These water molecules make specific hydrogen bonds to the DNA bases, the DNA phosphate backbones, and several critical Smad3 residues. In addition, the MH1 domain is found to contain a bound zinc atom using four invariant residues among Smad proteins, three cysteines and one histidine. Removal of the zinc atom results in compromised DNA binding activity. These results define the Smad MH1 domain as a zinc-coordinating module that exhibits unique DNA binding properties.

PubMed: 12686552
DOI: 10.1074/jbc.C300134200

実験手法

X-RAY DIFFRACTION (2.4 Å)