Structural basis of the interaction between BCL9-Pygo and LDB-SSBP complexes in assembling the Wnt enhanceosome

doi:10.1038/s41467-023-39439-9

	Structural basis of the interaction between BCL9-Pygo and LDB-SSBP complexes in assembling the Wnt enhanceosome
	Wang, Hongyang1 ; Bienz, Mariann 2; Yan, Xiao-Xue 3; Xu, Wenqing1
	2023-06-22
发表期刊	NATURE COMMUNICATIONS
EISSN	2041-1723
卷号	14 期号:1
发表状态	已发表
DOI	10.1038/s41467-023-39439-9
摘要	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 beta-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/beta-catenin signaling. Analysis of human cell lines lacking LDB or Pygo supports the functional relevance of the Pygo-LDB1-SSBP2 interaction for Wnt/beta-catenin-dependent transcription.
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收录类别	SCI
语种	英语
资助项目	Chinese Academy of Sciences Pilot Strategic Science and Technology Projects B grant[XDB37030302] ; National Laboratory of Biomacromolecules grant[2021kf01] ; National Natural Science Foundation of China["32000862","32171218"] ; China Postdoctoral Science Foundation[BX20200351] ; Cancer Research UK program["C7379/A8709","C7379/A15291","C7379/A24639"]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:001058061100034
出版者	NATURE PORTFOLIO
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/337722
专题	生命科学与技术学院生命科学与技术学院_PI研究组_许文青组
通讯作者	Yan, Xiao-Xue; Xu, Wenqing
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 2.Med Res Council Lab Mol Biol, Cambridge CB2 0QH, England 3.Chinese Acad Sci, Ctr Excellence Biomacromol, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Wang, Hongyang,Bienz, Mariann,Yan, Xiao-Xue,et al. Structural basis of the interaction between BCL9-Pygo and LDB-SSBP complexes in assembling the Wnt enhanceosome[J]. NATURE COMMUNICATIONS,2023,14(1).
APA	Wang, Hongyang,Bienz, Mariann,Yan, Xiao-Xue,&Xu, Wenqing.(2023).Structural basis of the interaction between BCL9-Pygo and LDB-SSBP complexes in assembling the Wnt enhanceosome.NATURE COMMUNICATIONS,14(1).
MLA	Wang, Hongyang,et al."Structural basis of the interaction between BCL9-Pygo and LDB-SSBP complexes in assembling the Wnt enhanceosome".NATURE COMMUNICATIONS 14.1(2023).