4CDK

Structure of ZNRF3-RSPO1

4CDK の概要

• エントリーDOI: 10.2210/pdb4cdk/pdb
• 関連するPDBエントリー: 4CDJ
• 分子名称: E3 UBIQUITIN-PROTEIN LIGASE ZNRF3, R-SPONDIN-1 (3 entities in total)
• 機能のキーワード: ligase, wnt signaling, adult stem cells, e3 ligase, protease-associated domain, zinc ring finger, lgr5, r-spondin
• 由来する生物種: MUS MUSCULUS (HOUSE MOUSE); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 126772.38

構造登録者

Peng, W.C.,de Lau, W.,Madoori, P.K.,Forneris, F.,Granneman, J.C.M.,Clevers, H.,Gros, P. (登録日: 2013-11-01, 公開日: 2014-01-08, 最終更新日: 2024-10-16)

主引用文献

Peng, W.C.,De Lau, W.,Madoori, P.K.,Forneris, F.,Granneman, J.C.M.,Clevers, H.,Gros, P.
Structures of Wnt-Antagonist Znrf3 and its Complex with R-Spondin 1 and Implications for Signaling.
Plos One, 8:83110-, 2013

PubMed Abstract: Zinc RING finger 3 (ZNRF3) and its homolog RING finger 43 (RNF43) antagonize Wnt signaling in adult stem cells by ubiquitinating Frizzled receptors (FZD), which leads to endocytosis of the Wnt receptor. Conversely, binding of ZNRF3/RNF43 to LGR4-6 - R-spondin blocks Frizzled ubiquitination and enhances Wnt signaling. Here, we present crystal structures of the ZNRF3 ectodomain and its complex with R-spondin 1 (RSPO1). ZNRF3 binds RSPO1 and LGR5-RSPO1 with micromolar affinity via RSPO1 furin-like 1 (Fu1) domain. Anonychia-related mutations in RSPO4 support the importance of the observed interface. The ZNRF3-RSPO1 structure resembles that of LGR5-RSPO1-RNF43, though Fu2 of RSPO1 is variably oriented. The ZNRF3-binding site overlaps with trans-interactions observed in 2:2 LGR5-RSPO1 complexes, thus binding of ZNRF3/RNF43 would disrupt such an arrangement. Sequence conservation suggests a single ligand-binding site on ZNRF3, consistent with the proposed competing binding role of ZNRF3/RNF43 in Wnt signaling.

PubMed: 24349440
DOI: 10.1371/JOURNAL.PONE.0083110

実験手法

X-RAY DIFFRACTION (2.8 Å)