Mechanistic and evolutionary insights into isoform-specific 'supercharging' in DCLK family kinases.

ABSTRACT: Catalytic signaling outputs of protein kinases are dynamically regulated by an array of structural mechanisms, including allosteric interactions mediated by intrinsically disordered segments flanking the conserved catalytic domain. The Doublecortin Like Kinases (DCLKs) are a family of microtubule-associated proteins characterized by a flexible C-terminal autoregulatory 'tail' segment that varies in length across the various human DCLK isoforms. However, the mechanism whereby these isoform-specific variations contribute to unique modes of autoregulation is not well understood. Here, we employ a combination of statistical sequence analysis, molecular dynamics simulations and in vitro mutational analysis to define hallmarks of DCLK family evolutionary divergence, including analysis of

SUBMITTER: Venkat A 

PROVIDER: S-EPMC10081240 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature