title: Disruption of TAB1/p38α interaction using a cell-permeable peptide limits myocardial ischemia/reperfusion injury.
abstract: Targeting the adaptor protein (transforming growth factor-β (TGF-β)-activated protein kinase 1 (TAK1)-binding protein 1) (TAB1)-mediated non-canonical activation of p38α to limit ischemia/reperfusion (I/R) injury after an acute myocardial infarction seems to be attractive since TAB1/p38α interaction occurs specifically in very limited circumstances and possesses unique structural basis. However, so far no TAB1/p38α interaction inhibitor has been reported due to the limited knowledge about the interfaces. In this study, we sought to identify key amino acids essential for the unique mode of interaction with computer-guided molecular simulations and molecular docking. After validation of the predicted three-dimensional (3-D) structure of TAB1/p38α complex, we designed several peptides and evaluated whether they could block TAB1/p38α interaction with selectivity. We found that a cell-permeable peptide worked as a selective TAB1/p38α interaction inhibitor and decreased myocardial I/R injury. To our knowledge, this is the first TAB1/p38α interaction inhibitor.
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, P.R. China.
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Wang
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhang
authors.forename: Dalin
authors.initials: D
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhu
authors.forename: Wendie
authors.initials: W
authors.lastname: Wang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Jin
authors.forename: Junxia
authors.initials: J
authors.lastname: Cao
authors.forename: Xinying
authors.initials: X
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.forename: Jiyan
authors.initials: J
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004195:Disease Models, Animal; D006801:Humans; D048308:Mitogen-Activated Protein Kinase 14 / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D051381:Rats
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010455:Peptides; C486300:TAB1 protein, human; D048308:Mitogen-Activated Protein Kinase 14