4C8V

Xenopus RSPO2 Fu1-Fu2 crystal form I

4C8V の概要

• エントリーDOI: 10.2210/pdb4c8v/pdb
• 関連するPDBエントリー: 4C84 4C85 4C86 4C8A 4C8C 4C8F 4C8P 4C8T 4C8V 4C8W 4C99 4C9A 4C9E 4C9R 4C9U 4C9V
• 分子名称: R-SPONDIN-2 (2 entities in total)
• 機能のキーワード: signaling protein, wnt, znrf3, rnf43, lgr4, lgr5, lgr6, rspo, r-spo, rspo1, rspo3, rspo4, receptor, membrane, signalling
• 由来する生物種: XENOPUS (SILURANA) TROPICALIS (WESTERN CLAWED FROG)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 110253.99

構造登録者

Zebisch, M.,Jones, E.Y. (登録日: 2013-10-01, 公開日: 2013-11-20, 最終更新日: 2019-10-16)

主引用文献

Zebisch, M.,Xu, Y.,Krastev, C.,Macdonald, B.T.,Chen, M.,Gilbert, R.J.C.,He, X.,Jones, E.Y.
Structural and Molecular Basis of Znrf3/Rnf43 Transmembrane Ubiquitin Ligase Inhibition by the Wnt Agonist R-Spondin.
Nat.Commun., 4:2787-, 2013

PubMed Abstract: The four R-spondin (Rspo) proteins are secreted agonists of Wnt signalling in vertebrates, functioning in embryogenesis and adult stem cell biology. Through ubiquitination and degradation of Wnt receptors, the transmembrane E3 ubiquitin ligase ZNRF3 and related RNF43 antagonize Wnt signalling. Rspo ligands have been reported to inhibit the ligase activity through direct interaction with ZNRF3 and RNF43. Here we report multiple crystal structures of the ZNRF3 ectodomain (ZNRF3(ecto)), a signalling-competent Furin1-Furin2 (Fu1-Fu2) fragment of Rspo2 (Rspo2(Fu1-Fu2)), and Rspo2(Fu1-Fu2) in complex with ZNRF3(ecto), or RNF43(ecto). A prominent loop in Fu1 clamps into equivalent grooves in the ZNRF3(ecto) and RNF43(ecto) surface. Rspo binding enhances dimerization of ZNRF3(ecto) but not of RNF43(ecto). Comparison of the four Rspo proteins, mutants and chimeras in biophysical and cellular assays shows that their signalling potency depends on their ability to recruit ZNRF3 or RNF43 via Fu1 into a complex with LGR receptors, which interact with Rspo via Fu2.

PubMed: 24225776
DOI: 10.1038/NCOMMS3787

実験手法

X-RAY DIFFRACTION (2.2 Å)