1IJY

CRYSTAL STRUCTURE OF THE CYSTEINE-RICH DOMAIN OF MOUSE FRIZZLED 8 (MFZ8)

1IJY の概要

• エントリーDOI: 10.2210/pdb1ijy/pdb
• 関連するPDBエントリー: 1IJX
• 分子名称: FRIZZLED HOMOLOG 8 (2 entities in total)
• 機能のキーワード: wnt receptor, frizzled protein structure, cysteine-rich, signaling protein
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Membrane; Multi-pass membrane protein: Q61091
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29886.12

構造登録者

Dann III, C.E.,Hsieh, J.C.,Rattner, A.,Sharma, D.,Nathans, J.,Leahy, D.J. (登録日: 2001-05-01, 公開日: 2001-07-11, 最終更新日: 2024-10-30)

主引用文献

Dann III, C.E.,Hsieh, J.C.,Rattner, A.,Sharma, D.,Nathans, J.,Leahy, D.J.
Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains.
Nature, 412:86-90, 2001

PubMed Abstract: Members of the Frizzled family of seven-pass transmembrane proteins serve as receptors for Wnt signalling proteins. Wnt proteins have important roles in the differentiation and patterning of diverse tissues during animal development, and inappropriate activation of Wnt signalling pathways is a key feature of many cancers. An extracellular cysteine-rich domain (CRD) at the amino terminus of Frizzled proteins binds Wnt proteins, as do homologous domains in soluble proteins-termed secreted Frizzled-related proteins-that function as antagonists of Wnt signalling. Recently, an LDL-receptor-related protein has been shown to function as a co-receptor for Wnt proteins and to bind to a Frizzled CRD in a Wnt-dependent manner. To investigate the molecular nature of the Wnt signalling complex, we determined the crystal structures of the CRDs from mouse Frizzled 8 and secreted Frizzled-related protein 3. Here we show a previously unknown protein fold, and the design and interpretation of CRD mutations that identify a Wnt-binding site. CRDs exhibit a conserved dimer interface that may be a feature of Wnt signalling. This work provides a framework for studies of homologous CRDs in proteins including muscle-specific kinase and Smoothened, a component of the Hedgehog signalling pathway.

PubMed: 11452312
DOI: 10.1038/35083601

実験手法

X-RAY DIFFRACTION (1.35 Å)