Disruption of TAB1/p38α Interaction Using a Cell-permeable Peptide Limits Myocardial Ischemia/Reperfusion Injury
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 threedimensional (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.
Qingyang Wang Junxia Cao Xinying Li Hui Peng Yan Li Beifen Shen Jiyan Zhang Jiannan Feng Jing Wang Xueying Zhang Dalin Zhang Ting Zhu Wendie Wang Xiaoqian Wang Jianfeng Jin
Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, P.R.China
国内会议
苏州
英文
139-148
2014-10-26（万方平台首次上网日期，不代表论文的发表时间）