Crystal structure of the p38α MAP kinase in complex with a docking peptide from TAB1

摘要

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.