A domain-swapped CaMKII conformation facilitates linker-mediated allosteric regulation.

ABSTRACT: Memory formation, fertilization, and cardiac function rely on precise Ca²⁺ signaling and subsequent Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) activation. Ca²⁺ sensitivity of the four CaMKII paralogs in mammals has been linked to the length of the variable linker region that is a hot spot for alternative splicing. In this study, we determined that the position of charged residues within the linker modulates the Ca²⁺/CaM sensitivity. We present an X-ray crystal structure of the full-length CaMKIIδ holoenzyme consisting of domain-swapped dimers within a dodecameric complex. In this structure, the kinase domain of one subunit is docked onto the hub domain of an adjacent subunit, providing an additional interface within the holoenzyme. Muta

SUBMITTER: Nguyen BV 

PROVIDER: S-EPMC10996533 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature