9RD6

Crystal structure of the 4CHRD domain of human chordin with Anderson-Evans polyoxotungstate

9RD6 の概要

• エントリーDOI: 10.2210/pdb9rd6/pdb
• 関連するPDBエントリー: 9IGM 9QVV
• 分子名称: Chordin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: chordin, chrd, 4chrd, extracellular, bmp, heparin, glycosaminoglycans, superoxide dismutase, protein transport
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 218772.60

構造登録者

Snee, M.,Baldock, C. (登録日: 2025-06-01, 公開日: 2026-06-17, 最終更新日: 2026-06-24)

主引用文献

Snee, M.,Birchenough, H.L.,Becker, M.H.,Popplewell, J.F.,Ashe, H.L.,Baldock, C.
Structural and biophysical analysis of the four CHRD domains of human chordin reveals a novel binding site for glycosaminoglycans.
J.Biol.Chem., :113248-113248, 2026

PubMed Abstract: Chordin is a cysteine-rich protein which acts as a regulator of bone morphogenetic protein (BMP) signalling in the extracellular matrix. Acting in concert with twisted gastrulation (TWSG1), chordin works as an antagonist of BMP signalling by binding tightly to the growth factor and is a vital component of the network of interactions that establish developmental signalling gradients. Chordin is known to interact with BMP ligands via its four von-Willebrand factor type C domains, but the function of the large central four CHRD domains were previously unknown. Here we show that these domains interact strongly with sulphated glycosaminoglycans (GAGs) and provide evidence for the location of the binding site using X-ray crystallographic analysis combined with mutagenesis and biophysical techniques. Additionally, we report the first recombinant expression and purification of the complete functional chordin, TWSG1, BMP2, BMP7 complex which was used to demonstrate that the four CHRD domains are largely redundant with respect to the role of chordin as an inhibitor of BMP ligands. We therefore propose that the four CHRD domains of chordin have relevance in the diffusion and localisation of chordin-TWSG1-BMP complexes at the tissue and organismal level, mediated by their interaction with GAGs or proteoglycans.

PubMed: 42285510
DOI: 10.1016/j.jbc.2026.113248

実験手法

X-RAY DIFFRACTION (3.28 Å)