Asymmetric coevolution of the MEK-ERK binding interface.

ABSTRACT: The highly conserved extracellular signal-regulated kinase (ERK) regulates diverse cellular processes by phosphorylating a wide range of intracellular substrates. Its catalytic activity relies on phosphorylation by a single upstream kinase, mitogen-activated protein kinase kinase (MEK), which interacts with only a few binding partners. Here, we test whether the asymmetry in protein-protein interaction network architecture influences the coevolution of the MEK-ERK complex. Phylogenetic sequence analysis across metazoan species revealed accelerated divergence in MEK's intrinsically disordered N-terminal docking motif (docking site [D-site]), whereas ERK remained highly conserved. Structure prediction with AlphaFold2 and extensive molecular dynamics simulations showed that five conserved D-si

SUBMITTER: Persikov AV 

PROVIDER: S-EPMC12550783 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature