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 splice

SUBMITTER: Venkat A 

PROVIDER: S-EPMC10602587 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature