8HIB

The crystal structure of Pygo2-LDB1-SSBP2 triple complex

Summary for 8HIB

• Entry DOI: 10.2210/pdb8hib/pdb
• Descriptor: LIM domain-binding protein 1, Single-stranded DNA-binding protein 2, Pygopus homolog 2, ... (4 entities in total)
• Functional Keywords: protein binding, complex, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 51986.94

Authors

Wang, H.Y.,Yan, X.X.,Xu, W.Q. (deposition date: 2022-11-19, release date: 2023-11-22, Last modification date: 2024-12-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.45 Å)