Activation Loop Dynamics Are Coupled to Core Motions in Extracellular Signal-Regulated Kinase-2.

ABSTRACT: The activation loop segment in protein kinases is a common site for regulatory phosphorylation. In extracellular signal-regulated kinase 2 (ERK2), dual phosphorylation and conformational rearrangement of the activation loop accompany enzyme activation. X-ray structures show the active conformation to be stabilized by multiple ion pair interactions between phosphorylated threonine and tyrosine residues in the loop and six arginine residues in the kinase core. Despite the extensive salt bridge network, nuclear magnetic resonance Carr-Purcell-Meiboom-Gill relaxation dispersion experiments show that the phosphorylated activation loop is conformationally mobile on a microsecond to millisecond time scale. The dynamics of the loop match those of previously reported global exchange within the kina

SUBMITTER: Iverson DB 

PROVIDER: S-EPMC7867030 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature