Skip to main content
eScholarship
Open Access Publications from the University of California

Molecular mechanism of activation-triggered subunit exchange in Ca2+/calmodulin-dependent protein kinase II

  • Author(s): Bhattacharyya, M
  • Stratton, MM
  • Going, CC
  • McSpadden, ED
  • Huang, Y
  • Susa, AC
  • Elleman, A
  • Cao, YM
  • Pappireddi, N
  • Burkhardt, P
  • Gee, CL
  • Barros, T
  • Schulman, H
  • Williams, ER
  • Kuriyan, J
  • et al.
Abstract

© Bhattacharyya et al. Activation triggers the exchange of subunits in Ca2+/calmodulin-dependent protein kinase II (CaMKII), an oligomeric enzyme that is critical for learning, memory, and cardiac function. The mechanism by which subunit exchange occurs remains elusive. We show that the human CaMKII holoenzyme exists in dodecameric and tetradecameric forms, and that the calmodulin (CaM)-binding element of CaMKII can bind to the hub of the holoenzyme and destabilize it to release dimers. The structures of CaMKII from two distantly diverged organisms suggest that the CaM-binding element of activated CaMKII acts as a wedge by docking at intersubunit interfaces in the hub. This converts the hub into a spiral form that can release or gain CaMKII dimers. Our data reveal a three-way competition for the CaM-binding element, whereby phosphorylation biases it towards the hub interface, away from the kinase domain and calmodulin, thus unlocking the ability of activated CaMKII holoenzymes to exchange dimers with unactivated ones.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Main Content
Current View