title: Crystal structure of the p38α MAP kinase in complex with a docking peptide from TAB1.
abstract: The mitogen-activated protein kinase (MAPK) p38α is a key regulator in many cellular processes, whose activity is tightly regulated by upstream kinases, phosphatases and other regulators. Transforming growth factor-β activated kinase 1 (TAK1) is an upstream kinase in p38α signaling, and its full activation requires a specific activator, the TAK1-binding protein (TAB1). TAB1 was also shown to be an inducer of p38α's autophosphorylation and/or a substrate driving the feedback control of p38α signaling. Here we determined the complex structure of the unphosphorylated p38α and a docking peptide of TAB1, which shows that the TAB1 peptide binds to the classical MAPK docking groove and induces long-range conformational changes on p38α. Our structural and biochemical analyses suggest that TAB1 is a reasonable substrate of p38α, yet the interaction between the docking peptide and p38α may not be sufficient to trigger trans-autophosphorylation of p38α.
authors.affiliation: Tsinghua-Peking Center for Life Sciences and MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Xin
authors.forename: Jiawei
authors.initials: J
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000737:chemistry; D051379:Mice; D048308:Mitogen-Activated Protein Kinase 14 / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020930:MAP Kinase Kinase Kinases; D048308:Mitogen-Activated Protein Kinase 14; D010455:Peptides; D000099151:MAP Kinase Kinase Kinase 7; C486300:TAB1 protein, human; C531463:Tab1 protein, mouse