Sequence- and Docking-Site-Dependent Contributions to Multi-Site Phosphorylation of an Intrinsically Disordered MAPK Substrate.

ABSTRACT: Protein kinases often rely on docking site motifs to enhance substrate interactions and facilitate phosphorylation. For example, mitogen-activated protein kinases (MAPKs) utilize D- and F-motifs, which frequently act in concert to enable bipartite substrate binding. While these motifs are known to modulate phosphorylation efficiency, their quantitative impact on target site phosphorylation within long intrinsically disordered substrates remains largely unexplored. Using NMR spectroscopy, JNK1-dependent phosphorylation of JIP1, a 450-amino acid disordered substrate, is investigated, identifying eleven phosphosites with distinct phosphorylation efficiencies. By selectively disrupting JNK1 binding to the D- and F-motifs of JIP1, the determinants of phosphorylation efficiency are uncovered. Sp

SUBMITTER: Orand T 

PROVIDER: S-EPMC12463012 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature