8HIB

The crystal structure of Pygo2-LDB1-SSBP2 triple complex

8HIB の概要

• エントリーDOI: 10.2210/pdb8hib/pdb
• 分子名称: LIM domain-binding protein 1, Single-stranded DNA-binding protein 2, Pygopus homolog 2, ... (4 entities in total)
• 機能のキーワード: protein binding, complex, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 51986.94

構造登録者

Wang, H.Y.,Yan, X.X.,Xu, W.Q. (登録日: 2022-11-19, 公開日: 2023-11-22, 最終更新日: 2024-12-11)

主引用文献

Wang, H.,Bienz, M.,Yan, X.X.,Xu, W.
Structural basis of the interaction between BCL9-Pygo and LDB-SSBP complexes in assembling the Wnt enhanceosome.
Nat Commun, 14:3702-3702, 2023

PubMed Abstract: The Wnt enhanceosome is responsible for transactivation of Wnt-responsive genes and a promising therapeutic target for treatment of numerous cancers with Adenomatous Polyposis Coli (APC) or β-catenin mutations. How the Wnt enhanceosome is assembled remains poorly understood. Here we show that B-cell lymphoma 9 protein (BCL9), Pygopus (Pygo), LIM domain-binding protein 1 (LDB1) and single-stranded DNA-binding protein (SSBP) form a stable core complex within the Wnt enhanceosome. Their mutual interactions rely on a highly conserved N-terminal asparagine proline phenylalanine (NPF) motif of Pygo, through which the BCL9-Pygo complex binds to the LDB-SSBP core complex. Our crystal structure of a ternary complex comprising the N-terminus of human Pygo2, LDB1 and SSBP2 reveals a single LDB1-SSBP2 complex binding simultaneously to two Pygo2 molecules via their NPF motifs. These interactions critically depend on the NPF motifs which bind to a deep groove formed between LDB1 and SSBP2, potentially constituting a binding site for drugs blocking Wnt/β-catenin signaling. Analysis of human cell lines lacking LDB or Pygo supports the functional relevance of the Pygo-LDB1-SSBP2 interaction for Wnt/β-catenin-dependent transcription.

PubMed: 37349336
DOI: 10.1038/s41467-023-39439-9

実験手法

X-RAY DIFFRACTION (2.45 Å)