7CD1

Crystal structure of inhibitory Smad, Smad7

7CD1 の概要

• エントリーDOI: 10.2210/pdb7cd1/pdb
• 分子名称: Mothers against decapentaplegic homolog 7, SULFATE ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: mh2 domain, smad, tgf-beta, signal transduction, signaling protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 86889.56

構造登録者

Murayama, K.,Kato-Murayama, M.,Shirouzu, M. (登録日: 2020-06-18, 公開日: 2021-03-17, 最終更新日: 2023-11-29)

主引用文献

Murayama, K.,Kato-Murayama, M.,Itoh, Y.,Miyazono, K.,Miyazawa, K.,Shirouzu, M.
Structural basis for inhibitory effects of Smad7 on TGF-beta family signaling.
J.Struct.Biol., 212:107661-107661, 2020

PubMed Abstract: Smad6 and Smad7 are classified as inhibitory Smads (I-Smads). They are crucial in the fine-tuning of signals by cytokines of the transforming growth factor-β (TGF-β) family. They are negative feedback regulators and principally target the activated type I receptors as well as the activated Smad complexes, but with distinct specificities. Smad7 inhibits Smad signaling from all seven type I receptors of the TGF-β family, whereas Smad6 preferentially inhibits Smad signaling from the bone morphogenetic protein (BMP) type I receptors, BMPR1A and BMPR1B. The target specificities are attributed to the C-terminal MH2 domain. Notably, Smad7 utilizes two alternative molecular surfaces for its inhibitory function against type I receptors. One is a basic groove composed of the first α-helix and the L3 loop, a structure that is shared with Smad6 and receptor-regulated Smads (R-Smads). The other is a three-finger-like structure (consisting of residues 331-361, 379-387, and the L3 loop) that is unique to Smad7. The underlying structural basis remains to be elucidated in detail. Here, we report the crystal structure of the MH2 domain of mouse Smad7 at 1.9 Å resolution. The three-finger-like structure is stabilized by a network of hydrogen bonds between residues 331-361 and 379-387, thus forming a molecular surface unique to Smad7. Furthermore, we discuss how Smad7 antagonizes the activated Smad complexes composed of R-Smad and Smad4, a common partner Smad.

PubMed: 33166654
DOI: 10.1016/j.jsb.2020.107661

実験手法

X-RAY DIFFRACTION (1.89 Å)