{"title":"Structural insights into the binding of human TGIF1 with SMAD2 MH2 domain.","authors":"Heng Zhou, Zheyu Xu, Yue Xiong, Yuanyuan Zhang, Runchen Li, Xiaoling He, Rui Hu, Jiang Zhu, Yunhuang Yang, Maili Liu","doi":"10.1002/1873-3468.70073","DOIUrl":null,"url":null,"abstract":"<p><p>Homeobox protein TGIF1 plays crucial roles in human development and body functions, partly by functioning as a corepressor in TGFβ signaling pathway. TGIF1 interacts with the MH2 domain of SMAD2 and is subsequently recruited to SMAD-binding elements to repress TGFβ-responsive gene expression. Here, through NMR titration, HDX-MS, and AlphaFold3 modeling, we reveal that a vertebrate-conserved short motif (I302-L310) of TGIF1 binds to a groove on the surface of SMAD2-MH2. The TGIF1-binding sites of SMAD2 overlap with those for its coactivators. BiFC assays verified that α2-β8 loop of SMAD2-MH2 plays a key role in binding to TGIF1. This study provides structural insight into the mechanism by which TGIF1 acts as a corepressor of SMAD2, probably through competing with coactivators for binding.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEBS Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/1873-3468.70073","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0
Abstract
Homeobox protein TGIF1 plays crucial roles in human development and body functions, partly by functioning as a corepressor in TGFβ signaling pathway. TGIF1 interacts with the MH2 domain of SMAD2 and is subsequently recruited to SMAD-binding elements to repress TGFβ-responsive gene expression. Here, through NMR titration, HDX-MS, and AlphaFold3 modeling, we reveal that a vertebrate-conserved short motif (I302-L310) of TGIF1 binds to a groove on the surface of SMAD2-MH2. The TGIF1-binding sites of SMAD2 overlap with those for its coactivators. BiFC assays verified that α2-β8 loop of SMAD2-MH2 plays a key role in binding to TGIF1. This study provides structural insight into the mechanism by which TGIF1 acts as a corepressor of SMAD2, probably through competing with coactivators for binding.
期刊介绍：
FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
